Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to the privileged conditions of natural selection, marine natural products are subject to overcome the pressure put on identify novel drugs; not only in the case of newly discovered bioactive metabolites, but also in those previously known. Since drug resistance has caused an increase in infections caused by tuberculous and nontuberculous Mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a means to address this problem. In this sense, this study presents an evaluation of in vitro effect of laurinterol (1) and aplysin (2), two brominated sesquiterpenes isolated from Laurencia johnstonii against nine Mycobacterium tuberculosis strains and six nontuberculous mycobacteria. Laurinterol (1) exhibited good anti-tuberculous activity, especially against nontuberculous mycobacteria, being remarkable the effect against M. abscessus with MIC values lower than the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii, that can be considered an interesting lead compound for the discovery of novel antimycobacterial molecules to treat NTM infections.

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in the developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literatures from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Two-dimensional (2D) ice I is an atomic-level ice that is composed of two interlocked atom-ic layers saturated with hydrogen bonds. It has recently been experimentally observed but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2d ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not de-stroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it could be used as an anti-3D-icing agent under low tem-perature.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169, an inhibitor of the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1) in Mycobacterium tuberculosis (Mtb), showed anti-TB potential in animal model and piloted clinical tests. Although highly potent, the BTZ type DprE1 inhibitors in general shows extremely low aqueous solubility, which adversely affect the drug like property. To improve the compounds physiochemical properties, we generated a series of BTZ analogues. Several optimized compounds had MIC values against Mtb in single digit nanomolar. The representative compound 37 displayed improved solubility and bioavailability compared to the lead compound. Additionally, compound 37 shows Mtb-killing ability in an acute infection mouse model.

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of Essential oils with CYP17A1 and CYP19A1, and functional assays were done using the radiolabeled substrates or Liquid Chromatography high‑resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these Essential oils in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds, voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8), and conoduramine (9), were isolated from the stem bark of Voacanga africana. The structures of the compounds were determined by comprehensive spectroscopic analyses (1D- and 2D-NMR). Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC50 values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the the O. ochengi thioredoxin reductase target and docking simulation attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilirial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant anti-TB activity with an MIC₉₀ value of 1.5 μM.

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1-6, were designed, synthesized, and evaluated for their anticancer activity against BCL-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential Bcl-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared to 0.62 ± 0.01 µM for gossypol, employed as positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at G1/S phase. Importantly, U2 displayed a favorable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 compared to MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

Crocin, a glycoside carotenoid showing several health benefits, is mainly obtained from saffron (Crocus sativus L.), whose quality and content of phytochemicals can be strongly affected by environmental conditions. Therefore, in this work, the crocin content and the in vitro antioxidant activity of saffron extracts obtained from three different varieties (Greek, Sicilian, and Iranian saffron) were assessed. Crocin content in saffron extracts was quantified by ultra-performance liquid chromatography coupled with mass spectrometry. The antioxidant activity of saffron extracts was evaluated using the oxygen radical absorbance capacity (ORAC) assay and nitric oxide (NO) radical scavenging test. The Maillard reaction was used to assess the anti-glycation activity. Although the Sicilian and Iranian saffron extracts contained higher amounts of crocin compared to the Greek one, ORAC values and % NO inhibition were higher for the Greek variety that showed a total phenolic content about two-fold greater than that of the other two extracts. Sicilian and Greek saffron had similar anti-glycation activities, while the Iranian saffron was less effective. These results suggest that the antioxidant activity of saffron extracts could be ascribed to their naturally occurring complex mixture of phytochemicals, deserving further investigations as supplement to prevent pathological conditions induced by radical species.

Leishmaniasis is a group of neglected infectious, non-contagious diseases caused by parasites of the Leishmania genus which affects millions of people worldwide. The drugs available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated, have serious side effects and in many cases are ineffective due to the emergence of resistant strains. In this context, the search for new candidates for more effective and safer drugs which can become new therapeutic alternatives is a constant need. In this work, 10 new chalcones were synthesized in high yields through Claisen-Schmidt condensation and were evaluated in vitro against Leishmania infantum promastigotes and amastigotes. CP04 and CP06 compounds were the most promising, respectively showing IC50 values = 13.64 ± 0.25 and 11.19 ± 0.22 against promastigotes, and IC50 = 18.92 ± 0.05 and 22.42 ± 0.05 against amastigotes. The compounds did not show cytotoxicity in erythrocytes, showing selectivity indexes greater than 74 and 90. Molecular docking studies carried out under the sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from L. infantum evidenced the great affinity of the CP04 molecule for these targets, showing Moldock score values of -94.0758 and -50.5692 KJ/mol-1, with these values being much lower than the co-crystallized ligand energies. Molecular dynamics simulations demonstrated great stability of CP04 in its targets, thus indicating a real interaction possibility. Our findings confirm the potential that chalcones have as candidates for anti-leishmania drugs, and suggest that the CP04 compound may become a promising drug candidate to design and develop novel chalcone-based analogs for leishmaniosis therapy.

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in solution. The conjugation sites and ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. T6 (with double end AA-conjugation) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid–based therapeutics with improved drug delivery and biophysical and biological efficacy.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

Versatile hybrid organic polymers are prepared using two active intermediates such as cynuric chloride and chitosan derivatives. The prepared chalcones are characterized by using FT-IR, UV, and proton NMR, thermal analysis and Minimum inhibitory Concentration. Thermal stability of the synthesized hybrid polymer is found using TGA and the hybrid chitosan derivative chalcone is thermally stable up to 270 °C. The antimicrobial activity of the prepared chitosan containing chalcone moiety are find out using Minimum Inhibitory Concentration (MIC) method. The synthesized versatile chalcone shows excellent antimicrobial activity against gram-negative bacteria such as Pseudomonas aeruginosa; and Gram-positive bacteria Chalcone containing halogen moiety shows high activity (MIC 7.8 µg/mL) than the hydroxyl containing chalcone. Cytotoxicity activity of the synthesized composites shows high activity.

Tuberculosis (TB) is an infectious-contagious disease caused by M. tuberculosis (Koch’s bacillus). About one-quarter of the world’s population is infected with that bacillus and at risk of developing TB disease. Latent tuberculosis corresponds to people who have been infected by TB bacteria but are not (yet) ill. The most vulnerable population to TB activation includes HIV infected, drug abuse and autoimmune disease patients. Multiple Sclerosis (MS) is a chronic and autoimmune neurological disease caused by lymphocytic infiltration. Its prevalence worldwide is 22.2 million cases of MS. There is a relation between TB and MS: due to immunomodulation or immunosuppression treatment of MS (reactivation of latent infection), or due to the intense inflammatory response before the infection of the bacillus (increased susceptibility to the development of autoimmune diseases). Screening for TB includes complete patient history, physical exam, chest radiography, and Tuberculin Skin Test or IGRA (Interferon Gamma Release Assay). This investigation is suggested when MS drugs (immunomodulatory and immunosuppressant medications) are prescribed. If a patient has positive results, the treatment for MS should not be delayed for the finishing TB treatment. In this paper, considering the high prevalence of tuberculosis, we recommend that TB screening should be also done at the moment of Multiple Sclerosis diagnosis.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.

Tuberculosis (TB) associated with diabetes (DM) is a growing problem, particularly in low and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment with isoniazid (INH) or rifampicin (RIF) in people with DM. Participants were assigned six months of INH 300mg/day plus pyridoxine 75mg or three months of RIF 600mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TB preventive treatment is not safe enough to be considered a universal indication to patients with DM and LTBI. These results underline the need to search for alternative TB prevention in DM patients with better safety profiles.

This study evaluated the effects of high-temperature and high-pressure treatment on the antioxidant and anti-inflammatory activities of carrot extracts. The total polyphenol and flavonoid content of heated carrot extract increased as the heating temperature increased, with 403.93 mg GAE/100 g and 53.14 mg CE/100 g at 150°C. DPPH and ABTs radical scavenging activity (IC50) of heated carrot extract also increased as the heating temperature increased, with 4.65 mg/mL and 7.31 mg/mL, respectively, at 150°C. The reducing power increased with the heating temperature. Heated carrot extract did not exhibit any temperature- or concentration-dependent cytotoxicity. Nitric oxide (NO) generation was suppressed as the heating temperature and NO production increased. The heated carrot extract showed a decrease in the production of dose-dependent TNF-α, IL-1β, and IL-6 compared to the control group. The above results show that heated carrot extract had effective antioxidant and anti-inflammatory activities.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

Seaweeds, notably cochayuyo (Durvillaea incurvata), are recognized for their rich macro- and micronutrient content, along with their inhibitory effects on the α-glucosidase enzyme. The present study aims to evaluate the effectiveness of this inhibition in actual starchy food products under in vitro gastrointestinal conditions. The study utilized freeze-dried cochayuyo, extracted using hot pressurized liquid extraction with 50% ethanol at 120 C and 1500 psi. The inhibition mechanism of α-glucosidase was determined, and the polyphenol composition of the extract was analyzed using Ultra-High-Performance Liquid Chromatography. The study further evaluated the extract’s impact on starch digestibility, total phenolic content, and antioxidant capacity in noodles as representative starchy food under gastrointestinal conditions. The results indicate that the α-glucosidase inhibition mechanism is mixed. Phenolic compounds, primarily tetraphloroethol, could contribute to this anti-enzymatic activity. The extract was observed to decrease starch digestibility, indicated by a lower rate constant (0.0158 vs. 0.0261 min-1) and digested starch at an infinite time (77.4 vs. 80.5 g/100 g). A significant increase (~1200 vs. ~390 µmol TROLOX/100 g) in antioxidant activity was also noted during digestion when the extract was used. Thus, the study suggests that the cochayuyo extract can reduce starch digestion and enhance antioxidant capacity under gastrointestinal conditions.

Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

(1) Background: A history of TB is a known risk factor for long-term respiratory impairment affecting lung functions in both restrictive and obstructive lung disease. (2) Methods: We analyzed data from the NHANES 1 Epidemiologic Follow-up Study (NHEFS), a longitudinal study conducted on non-institutionalized adult US population, ages 25-74 years. Approximately 93 percent (n=13,383) of the cohort was successfully traced by the end of the survey period and was available for analysis. The final adjusted model included age groups, gender, family income, lifetime smoking, BMI, and frequency of alcohol consumption as potential confounders. (3) Results: Estimated hazards ratio of developing Emphysema during follow-up in individuals that had a past diagnosis of TB was 54% lower (95% CI = 0.35, 0.61) as compared to individuals with no past TB, after controlling for potential confounders and using proportional hazards regression appropriate to the complex sample design. The association, however, was not statistically significant (HR = 0.862, p-value = 0.38) when only self-reported history of TB was considered as the exposure. (4) Conclusion: Tuberculosis (self-reported or LTBI) was strongly (but inversely) associated with Emphysema incidence. The association was not statistically significant with only self-reported history of TB as exposure.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Four previously undescribed highly oxygenated diterpenoids (1–4), zeylleucapenoids A–D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily by NMR experiments. The absolute configuration of 1 was established by theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2−4 were assigned by theoretical ORD calculations. Zeylleucapenoid D (4), with an IC₅₀ value of 38.45 μM in RAW264.7 macrophages and nontoxic activity for zebrafish embryo, and obviously inhibited pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. Compound 4 inhibited of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated the possible mechanism of action for 4 may be bind to targets by hydrogen- and hydrophobic- bond interactions.

The recently reported microbial natural product N-benzoyl-tryptophane (1) along with twenty-two diverse known bioactive compounds were isolated from the marine Aspergillus terreus LGO13 after its re-cultivation using liquid culture fermentation. Structures of the isolated compounds were established on the basis of HR-ESIMS 1D/2D NMR spectroscopy, and comparison with literature data. The antimicrobial, cytotoxicity, and antiviral activities of the microbial extract and the obtained compounds were investigated using a set of microorganisms, cervix carcinoma KB-3-1, non-small cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulation was employed to explore the theoretical targets of the isolated metabolites as anti-SARS-CoV-2 agents. Chaetominine (2) seemed to be a potential candidate against papain-like protease (PLpro), one of the viral proteins being aimed by recent research as a possible target of anti-covid agents. Inspired by the MD results, we accordingly assessed the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2. Fumitremorgin C (6) showed a high selectivity index (SI = 20.3), while chaetominine (2) and azaspirofuran A (9) showed moderate selectivity index (SI = 6.6 and 3.2, respectively). These results showed a promising antiviral activity of Fumitremorgin C against SARS-CoV-2 virus.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their anti-tumor activity were evaluated in vitro both for activity optimization and structure-activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved anti-tumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of 6 carbon atoms with IC50 ranging from 1.11 to 2.80 μM on various cancer cell lines. Consistently, 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 are constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 μM without significant change in total STAT3 level. Moreover, 6e also suppressed the expressions of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 μM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body-weight loss. These results clearly indicate that 6e could be a potential anti-tumor agent by targeting JAK/STAT3 signaling pathway.

Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1^st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex₉GlcNAc₂ (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

In the interest of developing more effective and safer anti-Tuberculosis treatment, we aimed for a better understanding of the antimycobacterial action of ciprofloxacin against Mycobacterium tuberculosis (Mtb). We used GCxGC-TOF-MS and well described metabolomics statistical approaches, to investigate and compare the metabolic profiles of Mtb in the presence and absence of the drug. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol and triacylglycerol metabolism seen in this group, supports the previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, and the reduction in the glucogenic amino acids specifically, indicates a flux towards DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of actions of various drugs and possibly adaptations by Mtb resulting in resistance.

Shigellosis is a pathological condition that affects the digestive system to possibly cause diarrhoea. Shigella species, which are responsible for this disease, are highly contagious and spread through contaminated food and water. The increasing development of resistance by Shigella species necessitate the urgent need to search for new therapies against shigellosis causing diarrhoea. The scientific validation of medicinal plants, such as Diospyros gilletii, which is used for the traditional treatment of diarrhoeal conditions is worthwhile. The present study aims to investigate the antibacterial activity of extracts from D. gilletii against selected Shigella species. Extracts from D. gilletii stem bark were prepared by maceration using various solvents. An-tibacterial activity of D. gilletii extracts was evaluated on Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei using a microdilution method, whereas cytotoxicity test was performed on Vero and Raw cells using resazurin-based colorimetric assay. Bacterial membrane permeability studies were evaluated using pro-pidium iodide (PI) and 1-N-phenylnaphthylamine (NPN) uptake assays, whereas inhibition and eradica-tion tests on bacterial biofilms were carried out by spectrophotometry. As a result, methanol, ethanol and hydroethanol extracts of D. gilletii inhibited the growth of S. boydii, S. flexneri and S. sonnei with MIC values ranging from 125 to 500 µg/mL, without toxicity to Vero and Raw cells. Time kill kinetics revealed bacteri-cidal orientation at 2MIC and 4MIC, and bacteriostatic outcome at 1/2MIC. The mechanistic basis of anti-bacterial action revealed that D. gilletii extracts inhibited and eradicated Shigella biofilms, and promoted the accumulation of NPN and PI within the inner and outer membrane of bacteria to increase membrane per-meability, thereby causing membrane damage. This novel contribution toward the antibacterial and mech-anisms of action of D. gilletii extracts against Shigella species substantiate the use of this plant in the tradi-tional treatment of infectious diarrhoea.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Tuberculosis (TB) is an infectious disease of global public health importance, caused by the Mycobacterium tuberculosis complex. Despite advances in diagnosis and treatment, this disease has worsened with the emergence of multidrug-resistant strains of tuberculosis We aim to present and review the history, progress, and future directions in the diagnosis of tuberculosis by evaluating the current methods of laboratory diagnosis of tuberculosis, with a special emphasis on microscopic examination, cultivation on solid and liquid medium, as well as an approach to molecular assays. The microscopic method, although widely used, has its limitations, and the use and evaluation of other techniques are essential for a complete and accurate diagnosis. Bacterial culture, both in solid and liquid mediums, are essential methods in the diagnosis of TB. Culture on solid medium provides specificity and accuracy, while culture on liquid medium brings rapidity and increased sensitivity. Molecular tests such as LPA and Xpert MTB/RIF have been found to offer significant benefits in the rapid and accurate diagnosis of TB, including drug-resistant forms. These tests allow the identification of resistance mutations and provide essential information for choosing the right treatment. We conclude that combined diagnostic methods, using several techniques and approaches, provide the best result in the laboratory diagnosis of TB. Improving the quality and accessibility of tests, as well as the implementation of advanced technologies, is essential to help improve the sensitivity, efficiency, and accuracy of TB diagnosis.

Aim: Nepal’s medicinal plants are culturally important and have diverse benefits. Senna alata belongs to the family Leguminosae and is a valuable plant utilized for medicinal and ornamental purposes. The aim of the research was to extract Senna alata leaves by successive maceration with various solvents. Methods: In this study, various methods were utilized to evaluate phytochemistry, overall phenolic and flavonoid content, in-vitro antioxidant, anti-inflammatory, cytotoxicity assay, anti-thrombolytic activity, and antibacterial activities. Results: The extractive values of Senna alata were determined as 1.58%, 0.78%, and 5.92% in hexane, ethyl acetate, and methanol, respectively. GC-MS analysis revealed major compounds such as 3-Methylmannoside, Neophytadiene, Campesterol, and Vitamin E in the leaf extract. Qualitative phytochemical screening verified the tannin content, carbohydrates, flavonoids, cardiac glycosides, glycosides, and saponins in the methanol extract. The total phenolic and flavonoid values were 46.36±4.5 mg GAE/gm and 480.4±3.055 QE/gm of dried extract, respectively. The extract exhibited significant antioxidant and anti-inflammatory activities, with IC50 values of 29.81 and 9.93, respectively. Furthermore, it demonstrated cytotoxic activity with an LC50 value of 767.85 in the brine shrimp bioassay. In terms of thrombolytic activity, the extract showed clot lysis percentages of 7.89% and 10.13% at concentrations of 10 mg/ml and 25 mg/ml, respectively. Conclusion: In conclusion, the methanolic extract of Senna alata leaves displayed therapeutic potential, including antioxidant, anti-inflammatory, cytotoxic, thrombolytic, and antibacterial effects. The existence of several chemicals via GC-MS analysis also verified plant's potential for therapeutic use.

Malawi has developed an excellent, nation-wide system for monitoring people infected with HIV and keeping track of key epidemic markers. Their success lies in two things: the focus on simplicity and the use of data collection not only to track the epidemic and identify problems but also to give regular feedback and support to every clinic in the country. This achievement is the more remarkable given that Malawi is one of the poorest countries in the world, ranking 190 out of 194 countries by GDP, but has one of the most severe epidemics of HIV in the world, ranking 9th out of 168 countries by HIV prevalence. We first discuss the current state and likely future epidemic trends in Malawi: unless we know where we are and where we are going we cannot decide what to do or how to do it to in order to achieve a better outcome. We then discuss the history and development of Malawi’s patient monitoring system, as reported in their Integrated HIV Program Reports,ix which have been published quarterly since the beginning of 2004. We consider the current state of patient monitoring and support as reflected in the most recent report for the third quarter (Q3) of 2016 and comment on some of the questions that this raises. Finally, we consider ways in which the current system could be improved by strengthening Malawi’s analytical capacity and making better use of this unique data set. The focus here is on HIV in adultsv because if ART is initiated early in all adults living with HIV this should include testing all pregnant women for HIV and starting them on treatment immediately. However, PMTCT is especially important and care must be given to reducing MTCT and identifying the long-term child survivors of mother-to-child transmission and this demands a complementary assessment. There is an ongoing debate about the relative merits of treatment and prevention in reducing transmission and it should be made clear that the primary reason for starting people on treatment early is that it is in the best interest of the individual patient to start treatment as soon as possible after becoming infected. Allowing a person’s immune system to deteriorate to any degree is not consistent with the clinician’s commitment to ‘first do no harm’ and even those with the highest CD4⁺ cell count are at a substantially increased risk of death. What matters, therefore, is to get as many people as possible onto ART, ensure that they remain virally suppressed, and consider prevention in this context.

Pulmonary tuberculosis (PTB) is one of the leading causes of death in developing countries. This global health burden is worsened by the emergence of multi-drug resistance, which calls for new interventions to address the pandemic and medicinal plants remain a source for the new interventions. This study aimed to investigate the in vitro immunomodulatory effects of three plants used traditionally for the treatment of PTB in the Eastern Cape Province of South Africa. Eradication of Mycobacterium. tuberculosis in the lung tissue, requires the pro-inflammatory M1 phenotype. Thus, a plant extract with a high potential for anti-tuberculosis effects is expected to produce a high concentration of nitric oxide (NO) as the indicator for the pro-inflammatory M1 phenotype. To test this effect, lipopolysaccharide-activated RAW 264.7 macrophages were cultured and treated with the ethanolic crude extracts of three plants: Anthrixia philycoides, Lippia javaniva, and Sanicula elata at concentrations of 50µg/ml, 100µg/ml, and 200 µg/ml. After 24h, 50µl Griess reagent was added to the plates and absorbance was measure at 540nm. A standard curve of sodium nitrite dissolved in culture media was used to determine the concentration of NO in each sample. The results showed Anthrixia philycoides, and Lippia javanica, as anti-inflammatory when compared with the positive control, while Sanicula elata pro-inflammatory, producing a high amount of NO, compared with the positive control. Our results revealed the polarizing activity of Sanicula elata on macrophages towards M1 phenotype, with evidence of the nitric oxide production, warranting further in-vivo investigations of medicinal plant for anti-TB activity.

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

ntroduction: Respiratory tract Infections are the greatest cause of death worldwide. Since its outbreak in 2019, the coronavirus pandemic (COVID-19) has been a challenge to humans in terms of treatment and prevention of this respiratory viral infection. The re-emergence of respiratory viral infections like influenza, pose a serious hazard to global public health because they occur seasonally. Creating broad-spectrum antiviral compounds for rapid action in the case of an outbreak crisis, as well as bioweapon defences, is critical. Human galectin-3 is found in high concentrations in activated T lymphocytes, epithelial and endothelial cells, and fibroblasts. ProLectin -I and ProLectin -M are both galectin antagonists. Blocking viral entry with a complex polysaccharide component "ProLectin-M" has downstream effects on viral reproduction enabling it to be used as a therapeutic tool and a safe alternative to conventional anti-viral medicines. Methods: In total, 3 cell based assays have been conducted to evaluate antiviral efficacy of ProLectin–I and ProLectin-M against SARS-CoV-2 virus, Influenza-A (H1N1), and human respiratory syncytial virus (hRSV) strain A2. ProLectin-M and ProLectin-I were evaluated for their anti-viral potency using SARS-CoV2 virus strain by viral RNA Extraction and qRT-PCR assays. The plaque assays were carried out to determine the antiviral activity of the test products (ProLectin-I and ProLectin-M) against ‘Influenza-A (H1N1)-A/PR/8/34 (TC adapted)’ and ‘Human respiratory syncytial virus (hRSV) strain A2’ in a cell based in vitro setting. As eference standard, "Oseltamivir Phosphate" and "Remdesivir" were used to determine antiviral activity of test products against H1N1 and hRSV strains respectively.Results: The IC_{50 of} ProLectin-M and ProLectin-I against SARS-CoV-2 virus was found to be 6248 ng/ml (6.2µg/ml) and 4207 ng/ml (4.2μg/ml) respectively. The CC₅₀ value was similar in both the test products i.e. >100 µg/ml. Against Influenza A (H1N1) strain, ProLectin-M exhibited 95 % reduction in the viral load at the test concentration of 21.8 µg/mL with an IC₅₀ value of 5.4 µg/mL whereas, ProLectin-I did not show any cytotoxicity till 250 µg/mL concentration. Against 'human respiratory syncytial virus (hRSV) strain A2, ProLectin-M exhibited 65 % reduction in the viral load at the test concentration of 43.75 µg/mL with an IC₅₀ value of 27.41 µg/mL whereas, ProLectin- I did not show any cytotoxicity till 250 µg/mL concentration. Conclusion: Both ProLectin-I and ProLectin-M have been reported to exhibit broad-spectrum antiviral activity in ‘in-vitro’ setting. ProLectin-M reducing influenza-A virus by 95% and hRSC strain A2 by 65%. To better understand broad spectrum antiviral activity of ProLectin-I and ProLectin-M, further pre-clinical research is warranted.

The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated, among them, four icetexanes, and one abietane (1–5), which are first reported. Their structures were established by spectroscopic means, mainly ¹H and ¹³C NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (µM) = 0.0.46 ± 0.05, and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (µM) = 0.08 ± 0.003, and 0.05 ± 0.003, as the positive control, respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as positive control, IC₅₀ (µM) = 31.7 ± 1.04. The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.

Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (MTB) and M. africanum (MAF) remains a major global health threat. The varying response of different host to contact with the TB bacteria, indicates the importance of host genetics in susceptibility to TB disease. We explored the association among selected human/host genomic variants and disease caused by the two causative pathogens in Ghana through a case control study. MTBC isolates (323) recovered from pulmonary TB patients recruited between 2016 and 2018 were genotyped using spoligotyping. A selection of 29 SNPs from MTB-related genes with high frequency among African populations were genotyped using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Associations between MTBC lineages and host variables were assessed using univariate and multivariate logistic regression. The prevalence of MTB and Maf among the participants were 79% and 21% respectively. Association analysis between the controls and MAF showed that rs2695342 variant on the SIC11A1 gene have the propensity to confer susceptibility to MAF infections (P = 0.093, OR = 8.35, 95% CI = 0.70 – 99.24) whilst the rs17048476 (P = 0.088, OR = 1.57, 95% CI = 0.93 – 2.63) and rs1482868 (P = 0.095, OR = 0.60, 95% CI = 0.33 – 1.09) were observed to be only suggestive. Our findings implicate SLC11A1 as a potential susceptibility gene of substantial interest for TB caused by MAF which is an important pathogen in West Africa and highlight the need for in-depth host pathogen studies in West Africa.

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive proper-ties, especially given the beneficial properties of its fruits in this regard. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. Extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary de-pending on the organ, with the highest amount of polyphenols found in the leaves extract. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.88 mgTE/g for leaves to 65.25 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.93 mg TE/g) and the highest level was found for the barberry leaves (140.49 mgTE/g). The oxygen radical absorption capacity test (ORAC) showed the lowest value for the stem (167.70 mgTE/g) and the highest level for the leaves (267.81 mgTE/g). The range of percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of flavonoids, TPC, TFC, and the content of selected flavonoids. For the first time, phenolic acids, flavonoid agly-cones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. For the first time, the following phenol-ic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris: 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, flavonoid glycosides: eleuthero-side E, rutin, isoquercitin, luteoloside, nar-cissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones: catechin, luteolin, and eriodictyol were determined qualitatively and quantitatively for the first time as well.

A new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via analyses of NOESY spectroscopy data, comparison of optical rotation values with those of restricticin derivatives reported and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.

Argulus is an ectoparasite that frequently infects goldfish, with severe effects and a high death rate. The use of plant extracts has been widely reported to have antiparasitic activities, including one of the solasodine compounds in sour eggplant extracts. This research evaluated the antiparasitic activities of Compositions A (Solanum ferox and Zingiber zerumbet extract at 400 and 200 ppm, respectively), B (SFE and Boesenbergia pandurata at 900 ppm), and C (single Solanum ferox at 400 ppm). The research stages comprised 1) isolation and analysis of solasodine content in sour eggplant extracts and its extract composition, 2) in vitro antiparasitic activities on Argulus sp. at doses of 50 and 100 ppm with a testing time of 60–240 minutes, and 3) in vivo antiparasitic activities on Argulus sp. on goldfish at a dose of 100 ppm and observation for 2–12 hours of medication. The results showed that sour eggplant extracts had a solasodine concentration of 7.151 mg/L, whereas the derivative compositions A, B, and C were 656, 485, and 295 ppm, respectively. The in vitro testing demonstrated that composition A was effective for killing approximately 80–100% of Argulus, whereas compositions B and C killed 80–90% and 60–70%, respectively. Viewed from the effectiveness for killing parasites, the result was excellent (above 50%). The in vivo medication test was continued using three extract compositions at a dose of 100 ppm. Compositions A, B, and C were found to be capable of releasing 81.33, 75.67, and 71.00 arguli, respectively, per fish. We concluded that the single SFE extract and a concoction with BPE and ZZE had reasonable antiparasitic activity, whereas the concoction of SFE and ZZE killed more Argulus parasites at a higher rate.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various drugs in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model information is based on three published manuscripts; therefore, this is a follow-up study. The model will also serve as a practical guide to monitor and evaluate epidemiological TB management plans.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various medications and antibiotics in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and con-trolling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model will also serve as a guide to monitor and evaluate epidemiological TB management plans.

Background: Although Tuberculosis (TB) is one of the oldest diseases known to mankind, many practitioners are still unaware of various aspects of management of TB including drug resistant TB. To be able to make an impact on the disease burden we need to understand the knowledge, attitude and practices (KAP) of practitioners, both in government and private sector, towards TB case management. Methodology: A random cross-sectional survey of 99 respondents to assess the KAP towards TB case management using a digital semi-structured questionnaire which was pre-tested and administered to allopathic practitioners from across States in North and Central India. Results: 77% responders were government doctors and 23% were private practitioners. Chest physicians accounted for 61% of the responders. 26% of government and 78% of private doctors relied on sources which are difficult to validate for their knowledge on drug resistant TB management. There were large variations seen in knowledge on modes of transmission, standard precautions, extent of drug resistant TB, diagnostics as well as treatment regimen for drug resistant TB. Conclusion: The knowledge of both sector doctors especially amongst private practitioners with respect to the awareness of extent, diagnosis, and treatment and infection control measures for drug resistant TB is suboptimal which translates to poor diagnostic, therapeutic and infection control choices amongst private practitioners. If India has to achieve the targets for TB Elimination by 2025, serious work needs to be done to upgrade the knowledge of the private sector doctors on drug resistant tuberculosis. The Ministry of Health and Family Welfare, GoI needs to have regular educational programs for the private practitioners coupled with awareness campaigns and frequent surveys to assess the knowledge, attitude and practices being followed in the private sector for TB management including drug resistant TB.

The lethal combination involving TB and HIV, known as 'syndemic’ diseases synergistically act upon one another to magnify the disease burden. Individuals on ART are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic markers still remain a grey area of investigation. Here, we reviewed the latest research developments in IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Aim. To identify factors associated with mortality with tuberculosis diagnosis in the indigenous population in Peru 2015-2019. Methods. Case-control study nested in a retrospective cohort, using the registry of persons belonging to indigenous peoples of the National Tuberculosis Prevention and Control Strategy of the Ministry of Health of Peru. A descriptive analysis was applied, and then bivariate and multiple logistic regression was used to evaluate associations between the variables and the outcome (live-deceased), the results were presented as OR with their respective 95% confidence intervals. Results. The mortality rate of the total indigenous population of Peru was 1.75 deaths per 100,000 indigenous people diagnosed with TB. The community of Kukama kukamiria - Yagua reported 505 (28.48%) individuals. The final logistic model showed that indigenous men (OR=1.93; 95% CI: 1.001-3.7), with a history of HIV prior to TB (OR=16.7; 95% CI: 4.7-58.7) and indigenous people in old age (OR=2.95; 95% CI: 1.5-5.7), are factors associated with a greater chance of dying from TB. Conclusions. It is important to reorient health services among indigenous populations, especially those related to improving the timely diagnosis and early treatment of TB-HIV co-infection, to ensure comprehensive care for this population, considering that they are vulnerable groups.

Background: Women in rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for Tuberculosis (TB). This study was conducted to assess the general understanding of TB and of access to healthcare for women, as a first step towards implementation of a gender responsive TB programme in TandoAllayar, a rural district of Pakistan. Methods: A total of 36 participants were interviewed. The focus group discussion guide comprised of questions on: (1) family/household dynamics (2) community norms (3) healthcare system (4) women’s access to healthcare (5) TB Awareness;, and (6) women’s access to TB Care. Results: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women’s health and inadequate presence of female health providers, were identified as barriers to access of healthcare for women, higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services. Conclusion: Significant barriers are faced by women in access to TB care in rural districts of Pakistan. Programme implementers in high burden countries, should shift towards improved gender-responsive TB programming.

Tuberculosis (TB) is an airborne infectious disease caused by organisms in the Mycobacterium tuberculosis (Mtb) complex. In many low and middle-income countries, TB remains a major cause of morbidity and mortality. Once a patient has been diagnosed with TB, it is critical that healthcare workers make the most appropriate treatment decision given the individual conditions of the patient and the likely course of the disease based on medical experience. Depending on the prognosis, delayed or inappropriate treatment can result in unsatisfactory results including the exacerbation of clinical symptoms, poor quality of life, and increased risk of death. This work benchmarks machine learning models to aid TB prognosis using a Brazilian health database of confirmed cases and deaths related to TB in the State of Amazonas. The goal is to predict the probability of death by TB thus aiding the prognosis of TB and associated treatment decision making process. In its original form, the data set comprised 36,228 records and 130 fields but suffered from missing, incomplete, or incorrect data. Following data cleaning and preprocessing, a revised data set was generated comprising 24,015 records and 38 fields, including 22,876 reported cured TB patients and 1,139 deaths by TB. To explore how the data imbalance impacts model performance, two controlled experiments were designed using (1) imbalanced and (2) balanced data sets. The best result is achieved by the Gradient Boosting (GB) model using the balanced data set to predict TB-mortality, and the ensemble model composed by the Random Forest (RF), GB and Multi-layer Perceptron (MLP) models is the best model to predict the cure class.

Molecular studies regarding regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humanity, and it is still a challenge to prevent and treat it. The control of the infection as well as its diagnosis are still complex, and treatments used are linked to several side effects. This study aimed to investigate miRNA’s expression profile to identify possible biomarkers for tuberculosis. We applied NGS techniques to investigate miRNA’s global expression profile from blood samples of infected patients with tuberculosis, their respective healthy physicians, and external healthy individuals as controls. Samples from 22 individuals run through a differential expression, target genes, gene set enrichment, and miRNA-gene network analysis. We observed 153 altered miRNAs, among which, only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results propose that miRNAs may be involved in immune modulation, regulating the repertoire of genes expressed in the immune system’s cells. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.

Introduction Tuberculosis is common in Pakistan. Due to various factors including socioeconomic factors, compliance is poor to anti-tuberculosis drugs, leading to resistance. We aim to determine the prevalence of Multidrug resistance (MDR) tuberculosis in Pakistani population.Methods A prospective observational study was conducted from April 1, 2019, to December 31, 2019, in the Pulmonology department of a tertiary care hospital in Pakistan. Culture and sensitivity were assessed using a sputum sample or, in cases of an absent sputum sample, from Broncho alveolar lavage.ResultsApproximately 71.3% percent patients who had tuberculosis were found to be resistant to Isoniazid and around 48.6% did not respond to Rifampin. Multi-drug resistant was found in 29.4% participants.ConclusionMulti-drug resistance tuberculosis is very prevalent in Pakistan, which may increase burden on health care system and may lead to various complications of tuberculosis.

The emergence of drug-resistant strains of M. tuberculosis (Mtb) and the phenomenon of phe-notypic tolerance to drugs challenge the goal of tuberculosis (TB) elimination worldwide. By using the ex vivo cultures of alveolar macrophages obtained from lung tissues of TB patients after intensive antimicrobial chemotherapy before surgery, different subpopulations of multi-drug-tolerant Mtb with a spectrum of phenotypic and growth features were identified in the same TB lesions. Our results indicative of not only passive mechanisms generating nonheritable resistance of Mtb to antibiotics, which are associated mainly with a lack of Mtb growth, but also some active mechanisms of Mtb persistence, such as cell wall and metabolic pathway remod-eling. In one of the subpopulations, non-acid-fast Mtb have undergone significant repro-gramming with the restoration of acid-fastness, lipoarabinomannan expression and replication in host cells of some patients after withdrawal of anti-TB drugs. Our data indicate the universal stress protein Rv2623 as a clinically relevant biomarker of Mtb that have lost acid-fastness in human lungs. The studies of Mtb persistence, dormancy, and resumption and the identification of biomarkers characterizing these phenomena are very important to develop vaccines and drug regimens with the individualized management of patients for overcoming the re-sistance/tolerance crisis in anti-TB therapy.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

Methicillin-resistant Staphylococcus aureus (MRSA) exerts a considerable concern in healthcare and the community. Globally MRSA strains cause numerous infections with high morbidity and mortality rates. The success of MRSA is a result of the extensive production of virulence factors. With the limited treatment options for the MRSA infection and growing resistance problem, an urgent call is needed to search for an alternative to antibiotics. One of the promising strategies is targeting the quorum sensing (QS) system, of the MRSA, by using a dendrimer loaded with kinase inhibitor peptide. This study formulates a poly-amidoamine dendrimers (PAMAM) G4 dendrimers loaded with Quorum Quencher (QQ), QQ3 peptide which is a Histidine Kinase inhibitor. The physicochemical properties of the formula were characterized using different in-vitro analysis method such as Zetasizer and transmission electron microscope (TEM). The antibacterial activity and anti-virulence effect of the formula was tested against MRSA and different mutant stains using growth assay, haemolysis assay and biofilm assay. Overall, QQ3-G4 complex showed antibacterial and anti-virulence activity and it can be a potential alternative treatment to overcome antimicrobial resistance and treat MRSA infection.

Surgical treatment of tuberculosis has been applied in the former Soviet Union more frequently than in other countries. On the contrary to the international practice, tuberculoma has been often operated. There has been a decreasing tendency since the last decades; but the surgery rate is still comparatively high. Surgeries were sometimes performed without preceding chemotherapy. Among others, an argument in favour of the early surgery was non-compliance increasing with time. Compulsory treatments of patients with Tb and/or alcoholism are discussed here. The factors predisposing to the use of invasive procedures with questionable indications included the partial isolation from international scientific community, insufficient consideration of the principles of informed consent, professional autonomy and scientific polemics, as well as paternalistic attitude to patients. The message of this preprint is that patients should not undergo operations to comply with doctrines. Evidence-based clinical indications must be determined individually.

Background Nigeria is among the top 5 countries that have the highest gap between people reported as diagnosed and estimated to have developed Tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high risk of TB transmission and targeted Active Case Finding (ACF) interventions. Leveraging community level data together with granular sociodemographic contextual information can unmask local hotspots which could be otherwise missed. This work evaluated if this approach helps to reach communities with higher numbers of undiagnosed TB. Methodology A retrospective analysis of the data generated from an ACF intervention program in 4 south-western states in Nigeria was conducted. Wards (the smallest administrative level in Nigeria) were subdivided into further smaller population clusters. ACF sites and their respective TB screening outputs were mapped to these population clusters. This data was then combined with open-source high resolution contextual data to train a Bayesian inference model. The model predicted TB positivity rates on the community level (population cluster level), and these were visualised on a customised geoportal for use by the local teams to identify communities at high risk of TB transmission and plan ACF interventions. The TB positivity yield (proportion) observed at model-predicted hotspots was compared with the yield obtained at other sites identified based on aggregated notification data. Results The yield in population clusters that were predicted to have high TB positivity rates by the model was at least 1.75 times higher (p-value <0.001) than the yield in other locations in all four states. Conclusion The community level Bayesian predictive model has the potential to guide ACF implementers to high TB positivity areas for finding undiagnosed TB in the communities, thus improving efficiency of interventions.

Menaquinone is one of the major lipoquinones involved in the respiratory chains of bacteria, which includes ubiquinone. Menaquinone is an essential component in the electron transfer process and ATP synthesis especially in some Gram-positive bacteria including Mycobacterium tuberculosis (M. Tb). However, mammals utilize ubiquinone in the analogous electron transfer processes, and do not synthesize menaquinone. In the biosynthesis of menaquinone, MenA is an important enzyme, which is involved in the conversion of 1,4-dihydroxy-2-napthoate to demethylmenaquinone via prenyl transferase activity. Therefore MenA is chosen as a drug target in determining the inhibitor. While designing and screening MenA inhibitors we observed that benzophenone derivatives showed high coordination with enzymes in transition state and interrupted the growth of M. Tb moderately. In addition, diphenyl ether derivatives also showed moderate MIC and IC50 results. Therefore, to improve the biological activity we synthesized a polymeric compound having both benzophenone and diphenyl ether groups. In addition, a hydrophilic functional group was introduced into the polymeric compound to enhance the biological activity. The synthesized polymeric inhibitor showed improved MIC and IC50 values to inhibit the M. tb infection.

Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. BTB is caused by Mycobacterium bovis (M. bovis) and has economic and public health significance. which has significant impact on the health of livestock and human. It has been significantly a cause for great economic loss in animal production. Associated risk factors contributed to the prevalence of the disease in cattle and its transmission. Moreover, the majority of cattle owners lack awareness about the disease and its public health significance. The presence of multiple hosts including wild animals, inefficient diagnostic techniques, absence of defined national controls and eradication programs could impede the control of bovine TB. Awareness rising about the disease, its transmission andzoonotic implication however, in Ethiopia Bovine Tuberculosis in Human-Livestock-Wildlife Interface is not well studied in the country and there were no studies concerning the burden of the disease between human ,animal and wild life which is of great importance for reduction and control measures. This paper aims to review the potential health and economic impact of bovine tuberculosis control in order to safeguard human and animal population in Ethiopia

Disseminated or military tuberculosis (TB) is defined as the presence of at least two non-contiguous sites of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation and spread of a latent focus or due to iatrogenic origin. Disseminated TB represents a life-threatening condition, especially in at-risk children and when the diagnosis and treatment are delayed. We report on a case of a 3-year old boy who presented with long-lasting unrecognised disseminated TB that was successfully managed in a low-resource setting.

Background: The COVID-19 pandemic has promoted a shortage of filtering facepiece respirators (FFRs) and the emergence of new FFRs brands. We aimed to determine the fit provided by in-use FFRs in Peruvian healthcare workers (HCWs) during the COVID-19 pandemic. Methods: We enrolled 279 HCWs from 37 primary healthcare centers with highest burden of care for TB in Peru, of which 263 were assessed using quantitative fit tests (QNFT). Results were expressed as real-time fit factor (rt-FF) and overall fit factor (overall-FF), which was categorized as ≥100 (optimal result), 50-99, and <50. Results: We identified 3M 1860 FFRs (33.1%), Xiantao Zhong Yi ZYB-11 FFRs (24.7%) and Makrite 9500 FFRs (20.5%), mainly. Eighty-seven HCWs (33.1%) had an optimal overall-FF, 27 (10.3%) between 50-99, and 149 (56.7%) less than 50. Of the 87 HCWs with optimal over-all-FF, 73 (83.9%) were 3M 1860 FFR. Of the 27 participants with overall-FF between 50-99, 7 (25.9%) were Makrite 9500, while of the 149 with overall-FF less than 50, 58 (38.9%), and 47 (31.5%) were Xiantao Zhong Yi ZYB-11 and Makrite 9500, respectively. Conclusion: The Xiantao Zhong Yi and Makrite FFRs do not adapt adequately to the face of Peruvian HCWs, most having fit factors less than 50.

Background Tuberculosis is a type of infectious disease that can cause death if treatment is not completed. the duration of tuberculosis treatment can reach 6 to 8 months so it really requires discipline when doing treatment. This makes tuberculosis patients in dire need of health information and social support which is very helpful in providing motivation, health information, and monitoring treatment from nurses. Aim of this literature review is to provide an overview of the The Role Of Nurses In Providing Social Support In Tuberculosis Treatment: Literature Review. Method is a literature review research, this study uses electronic database searches using keywords according to research questions from the online library PubMed, Content Science, and Science Direct. Result it was found that the role of nurses in the aspect of social support, namely in providing motivation, supervision, comfort, empathy, and information. this is very necessary for patients with tuberculosis at the time of treatment. Conclution social support is needed by tuberculosis patients who are currently undergoing treatment to provide motivation, health information, and as a nurse's supervision of patient adherence to tuberculosis treatment.

Tuberculosis (TB) is a contagious disease, caused by Mycobacterium tuberculosis (MTB) that has infected and killed a lot of people in the past. At present treatments against TB are available at a very low cost. Since these chemical drugs have many adverse effects on health, more attention is now given on the plant-derived phytochemicals as potential agents to fight against TB. In this study, 5 phytochemicals, 4-hydroxybenzaldehyde, benzoic acid, bergapten, psoralen, and p-hydroxybenzoic acid, are selected to test their potentiality, safety, and efficacy against two potential targets, the MTB RNA polymerase and enoyl-acyl carrier protein (ACP) reductase, the InhA protein, using various tools of in silico biology. The molecular docking experiment, drug-likeness property test, ADME/T-test, P450 SOM prediction, pharmacophore mapping, and modeling, solubility testing, DFT calculations, and PASS prediction study had confirmed that all the molecules had the good potentiality to inhibit the two targets. However, two agents, 4-hydroxybenzaldehyde and bergapten were considered as the best agents among the five selected agents and they also showed far better results than the two currently used drugs, that function in these pathways, rifampicin (MTB RNA polymerase) and isoniazid (InhA protein). These two agents can be used effectively to treat tuberculosis.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant (MDR) or rifampin-resistant (RR) tuberculosis (TB) also play an important role in generating evidence to guide MDR/RR TB Generally, summary exposure classifications (e.g., ‘ever versus never’, ‘exposed at baseline’) have been used to characterize drug exposure, in the absence of detailed longitudinal data on MDR-TB regimen These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers’ ability to answer the most relevant questions while accounting for known This paper highlights the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens and offers an overview of the data and analytic strategies required to do

Studies on Protein-Protein interactions (PPI) can be helpful for the annotation of unknown protein function and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years for the characterization of Mycobacterium tuberculosis PPI to further decipher TB pathogenesis. This review aims at compiling the most striking results based on in vivo methods (yeast and bacterial two-hybrid systems, protein complementation assays) for the specific study of PPI in mycobacteria. Moreover, newly developed methods, such as in-cell native mass resonance and proximity-dependent biotinylation identification, will have a deep impact on future mycobacterial research, as they are able to perform dynamic (transient interactions) and integrative (multiprotein complexes) analyses.

South Africa is afflicted with the worst epidemic of HIV in the world a legacy of the system of oscillating migrant labour in the region and the consequent social disruption that was the legacy of Apartheid. The initial response from the national government was slow and ineffective but once the magnitude of the epidemic became apparent the government began to respond. The investment in HIV- and TB-related activities in 2013 was R22 Bn or (US$2.5; 2013 exchange rate) of which the South Africa government contributed 80% and the Presidents Emergency Plan for AIDS Relief (PEPFAR) 17%. South Africa now has the more people on anti-retroviral therapy than any other country and treatment is being started much sooner after infection. Much of the best biomedical, virological, immunological, mathematical and social science around the treatment and prevention of HIV and AIDS and the associated epidemic of TB has been done by South African’s and their international collaborators. If the efforts to control the epidemic are maintained South Africa is on track to meet the UNAIDS 90-90-90target by 2020 and to End AIDS by 2030 in spite of the magnitude of the problem. While individual, patient level data are increasingly available, especially in the Western Cape, much greater efforts need to be made to ensure that the information collected in this way is used to give feedback and support to clinic staff, to ensure that health clinics are providing the best possible service, and to individual patients and people living with HIV to ensure that they are receiving the best possible care and support. South Africa needs to make better use of the rich and detailed data that are being collected from individual clinics and their patients to identify problems or difficulties at the clinic level and to ensure that individual patients are retained on treatment, are virally suppressed and receive the best possible care and support.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments and vulnerable biological status. We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022. The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases. In conclusion, the co-infection of COVID-19 had an impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.

Xpert MTB/RIF is rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to access the diagnostic precision of Xpert MTB/RIF assay to detect pulmonary and extra-pulmonary tuberculosis and to evaluate the performance for the detection of rifampicin resistance. Of 37695 samples, 7156(18.98%) were tuberculosis positive, 509(7.11%) were rifampicin-resistant. The sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay for PTB were 99.87% (95%CI:99.75-99.94), 99.92%(95%CI:99.88-99.95), 99.71%(95%CI:99.54-99.82),99.97%(95%CI:99.93-99.98),21.38% (95%CI:20.92-21.86),and 99.91%(95%CI:99.87-99.94), respectively. For EPTB, the sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay accounted for 99.45% (95%CI:98.73-99.82),99.84%(95%CI:99.73-99.92),98.70%(95%CI:97.73-99.25),99.93% (95%CI:99.84-99.97),10.64%(95%CI:9.99-11.31),and 99.80%(95%CI:99.68-99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, Xpert MTB/RIF had contradictory results for 20.5% of cases among patients with negative smear results and 54.9% of cases among patients with a high risk of Multidrug-resistant tuberculosis. Of 47 fluoroquinolone-resistant, 16.56% (26/157) of Multidrug-resistant tuberculosis isolates and 4.02% (20/498) isoniazid-resistant are fluoroquinolone-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among Rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

A Bacille Calmette-Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-days intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low, and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provided limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime-boost regimen, to help the induction of a stronger cellular immune response.

Bacillus Calmette-Guérin (BCG) is the only widely used prophylactic tuberculosis (TB) vaccine that can prevent severe TB in infants. However, it provides poor protection in adults, and therefore, there in ongoing research on new TB vaccines and immunization strategies with more durable immune effects. The recombinant BCG and BCG prime-protein booster are two important vaccine strategies that have recently been developed based on BCG and could improve immune responses. In this study, three immune strategies based on four protective antigens, namely, ESAT-6, CFP-10, nPPE18, and nPstS1, were applied to construct recombinant rBCG-EPCP009, EPCP009 subunit protein, and BCG prime-EPCP009 booster vaccine candidates. The short- and long-term immune effects after vaccination in Balb/c mice were evaluated based on humoral immunity, cellular immunity, and the ability of spleen cells to inhibit in vitro mycobacterial growth. At 8 and 12 weeks after the initial immunization, splenocytes from mice inoculated with the BCG prime-EPCP009 protein booster secreted higher levels of PPD- and EPCP009-specific IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, and IL-12 and had a higher IFN-γ⁺CD4⁺ TEM:IL-2⁺CD8⁺ TCM cell ratio than splenocytes from mice inoculated with the rBCG-EPCP009 and EPCP009 proteins. In addition, the EPCPE009-specific IgG2a/IgG1 ratio was slightly higher in the BCG prime-EPCP009 protein booster group than in the other two groups. The in vitro mycobacterial inhibition assay showed that the splenocytes of mice from the BCG prime-EPCP009 protein booster group exhibited stronger inhibition of Mycobacterium tuberculosis （M. tuberculosis）growth than the splenocytes of mice from the other two groups. These results indicate that the BCG prime-EPCP009 protein booster exhibited superior immunogenicity and M. tuberculosis growth inhibition to the parental BCG, rBCG-EPCP009, and EPCP009 proteins under in vitro conditions. Thus, the BCG prime-EPCP009 protein booster may be important for the development of a more effective adult TB vaccine.

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.