The objective of the study was to apply the principles of analytical quality by design (AQbD) to the analytical method for the determination of the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, by means of thin layer chromatography (TLC) with a Radio-TLC scanner, the same one that allows to evaluate the quality of the product. For the AQbD, the analytical objective profile (ATP), critical quality attributes (CQA), risk management, the method operable design region (MODR) were defined through the response surface methodology for method optimization using the MINITAB ® software, Control Strategy and the validation of the method where the parameters of selectivity, linearity, precision, robustness, detection limit, quantification limit, range and stability of the sample solution were evaluated. Under the experimental conditions, the conditions of the method were demonstrated by TLC-Scanner and optimization was carried out for an injection volume of 3 µL, radioactive concentration of 10 mCi/mL and carrier volume of 40 µL. It was statistically demonstrated that the method is selective for the 131I iodide band Rf of 0,8 and for the radiochemical impurity IO₃⁻ Rf of 0.6, linearity from 6,0 to 22.0 mCi/mL, intermediate precision with Global RSD of 0,624%, robustness with global RSD 0,101%, detection limit of 0,09 mCi/mL, quantification limit of 0.53 Ci/mL, conforming range, and stability of the sample solution evaluated over time 0, 2 and 20 hours with a global RSD of 0,362%, obtaining consistent results. The development of the method based on AQbD allowed the generation of a design space and an operational space with knowledge of all the characteristics and limitations of the method, likewise in all the operations the conformity of the tests to the acceptance criteria was verified. The validity of our method is concluded under the established conditions, suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services.

In recent years, the field of drug delivery has seen a significant shift towards the exploration and utilisation of nanoparticles (NPs) as versatile carriers for therapeutic agents. With its ability to provide exact control over NPs' characteristics, microfluidics has emerged as a potent platform for the efficient and controlled synthesis of NPs. Microfluidic devices designed for precise fluid ma-nipulation at the micro-scale offer a unique platform for tailoring NP properties, enabling en-hanced control over NP properties such as size, morphology and size distribution while ensuring high batch-to-batch reproducibility. Microfluidics can be used to produce liposomes, solid lipid nanoparticles, polymer-based NPs and lipid-polymer hybrid NPs, as well as a variety of inorganic NPs such as silica, metal, metal oxide, quantum dots and carbon-based NPs, offering precise control over composition and surface properties. Its unique precision in tailoring NP properties holds great promise for advancing NP-based drug delivery systems in both clinical and industrial set-tings. Although challenges with large-scale production still remain, microfluidics offers a trans-formative approach to NP synthesis. In this review, starting from the historical development of microfluidic systems, the materials used to create the systems, microfabrication methods and system components will be discussed in order to provide the reader with an overview of micro-fluidic systems. In the following, studies on the fabrication of nanoparticles such as lipid NPs, polymeric NPs and inorganic NPs in microfluidic devices are included.

Background: no reports have examined the profile of drug-induced dysphagia in detail. The goal of this study was to investigate if there are any differences in the profiles of drug-induced dysphagia. Methods: This study used the Japanese Adverse Drug Event Report (JADER) database. Further, reported odds ratios (RORs) were used to analyze data on adverse drug events from 2004 to 2021. The top ten drugs with the most drug-induced dysphagia occurrences were used as target drugs. The association between RORs and drug-induced dysphagia caused by the target drugs was evaluated, and the age distribution and time of onset of drug-induced dysphagia for each drug were compared. RORs were the primary endpoint. Moreover, age and time of onset of drug-induced dysphagia were secondary outcomes. Results: In total, 756,965 reports were analyzed. All the target drugs were associated with drug-induced dysphagia. Among them, cevimeline was a novel finding, as no dysphagia was observed during the clinical trial. For most drugs, the onset of drug-induced dysphagia was occurring within approximately 25 days of administration. However, even after long-term use, paroxetine and milnacipran were associated with drug-induced dysphagia. Conclusion: The onset profile of drug-induced dysphagia may differ from one drug to the next.

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on demand drug release. In this study, a hybrid nanosystem for tempera-ture and pH sensitive delivery was prepared from MCM-41 nanoparticles grafted with newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemi-cally modified by carboxyl groups attachment. Later, they were grafted with agar (AA) and vi-nylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hy-drophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in different pH media and at different temperatures. At tumor simulating conditions (40ºC and pH 4.0) doxoru-bicin was almost completely released within 72 hours. The biocompatibility of the proposed na-noparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanopar-ticles for temperature-sensitive and pH-triggered drug delivery at the tumor site.

Due to the low content, few studies are focused on the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (syn. Lamiophlomis rotata (Benth.) Kudô. This plant has been used to treat rheumatic arthritis and grasserie in China. However, such EOs may have important pharmacological activities such as anti-cancer. To identify the chemical markers (CM) in the EOs and evaluate their antioxidant activities (AAs), we firstly conduct a thoroughly investigation on their chemicals and AAs, to the best of our knowledge. Light yellow EOs with fresh and elegant smell are obtained by hydro-distillation with average yield 0.11% (volume mL/weight g). The crystals are separated from the EOs through cryoprecipitation, respectively. A total of 81 components are qualified and quantified in the EOs, crystals and EOs removed crystals, in which 44 ones are first reported. As for content, the main compounds are long-chain fatty acids (FAs) and their esters. The most abundant one n-hexadecanoic acid (palmitic acid, PA) accounting for 43.15-54.8%, 58.49-64.57% and 15.9-41.1%, in the EOs, crystals and EOs removed crystals, respectively. Seven compounds including PA, tetradecanoic acid, linoleic acid, oleic acid, methyl hexadecanoate, hexahydrofarnesyl acetone and phytol can be chosen a the CMs in these EOs. The AAs are evaluated through in vitro assays. PA presents pro-oxidant activities in a concentration dependence manner. Usually, the EOs removed crystals demonstrate stronger AAs, and the crystals demonstrate weaker AAs compared with that of the corresponding EOs, which is related to the different content of PA in these samples. This study can give some hints for the utilization of such EOs which are abundant in FAs such as PA.

Abstract: A punicalagin is a metabolic product of pomegranate fruits and peeled. We have compiled the recent literature review from different sources. The extract of pomegranate fruits and peel has been reported for health-beneficial properties in inflammation-associated chronic disease and the regulatory role in NF-KB, MAPK, IL-6/JAK/STAT3, and PI3K/AKT/mTOR signaling pathway. Punicalagin is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven biological/pharmacological activities like antioxidant, hepatoprotective, an-ti-atherosclerotic, anti-cancer, anti-neurological, anti-diabetic, and anti-digestive. The extracts have a rich source of hydrolyzable tannin and anthocyanin exhibiting strong anti-neoplastic properties. Anti-cancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reported. The punicalagin-induced redirection of the signal-transduction pathway from survival and proliferation into the cell cycle by arrested the living cells. Apoptosis senescence and autophagy and thus compromising neoplastic progression are delineated. This review is based mainly on data obtained from various sources including the in-vitro cell line model and its activities that are concerned with the effect of punicalagin activities on various cell types.

This study explored the potential synergism within chlorhexidine-silver nanoparticles conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively-charged nano-silver colloid (ζ=-50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ=+44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in the effects against S. aureus and C. albicans, and synergism against E. coli with minimal inhibitory concentrations of SN 5.5 µg/mL+Cx 8.8 µg/mL. The SN showed excellent, increasing with time, virucidal properties, and low toxicity. The coupling of the cationic chlorhexidine with nano-silver, however, did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and А549). The newly-synthesized antimicrobial agent presented with an extended and promising therapeutic spectrum and needs to be further evaluated on relevant to the designated route of administration three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

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.

Numerous studies have shown that quinolones residues in the foods exceeding the MRL is harmful to the human health. There are some limitations in the existing methods for the residues, so we developed a new limit test method (TLC-SERS) to rapidly determine following residues: enrofloxacin(A), ciprofloxacin (B), ofloxacin(C), fleroxacin(D), sparfloxacin(E), enoxacin(F), gatifloxacin(G) and nadifloxacin(H). The residues can be preliminarily separated by TLC. Labeling the tested compounds’ position on the thin layer plate by their relative Rf under 254nm ultraviolet, and an appropriate amount of nanometer silver solution should be added to the position. The silver on the plate should be irradiated with 532nm laser to obtain SERS of the compounds. The results showed a significant differences of the 8 quinolones’ SERS; the LOD of the H, A, D, E, C, G, F and B were orderly 9.0, 12.6, 8.0, 19.0, 8.0, 8.4, 9.0 and 12.6 ng/mL, and the RSD≤4.9% for SERS of each quinolones.The limit test results of the 20 samples was consistent with that determined by the UPLC–MS/MS. The above results indicate that the TLC-SERS is specific, sensitive, stable, and accurate, providing a new reference for the rapid limit test of harmful residues in foods.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. In two of them, the optimized geometry was determined in the monomer, cyclic dimer and staking forms using the B3LYP, M06-2X and MP2 methods. The effect of the para-substitution in the aryl ring was evaluated based on the changes in the molecular structure and atomic charge distribution of the triazole ring. Several relationships were obtained that could facilitate the selection of the substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to the functional calculations on the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE).

Tamanu oil has traditionally been used to treat various skin problems. The oil has wound-healing and skin-regenerating capabilities, and encourages the growth of new skin cells, all of which are helpful for fading scars and hyperpigmentation, as well as promoting an all-around glow. The strong nutty odor and high viscosity are the major disadvantages associated with their application. The aim of this study was to create bigels using tamanu oil for its anti-scarring properties. Bigels were prepared with Tamanu oil ranging from 5 to 20% along with micronized xanthan gum and evaluated for their pH, viscosity, and spreadability. In silico studies were performed to analyze the binding affinity of the protein with the drug, and the anti-scarring activity was established using a full-thickness excision wound model. In silico studies have reported that the components Calanolide A, Inophyllum C, and 4-Norlanosta-17(20),24-diene-11,16-diol-21-oic acid, and 3-oxo-16,21-lactone had docking scores of -9.8, -11.3, and -11.1, respectively with the cytokine TGF- β1 receptor. An acute dermal irritation study in rabbits showed no irritation, erythema, eschar, or edema. In vivo excisional wound healing studies performed on wistar rats and subsequent histopathological studies showed that bigels had better healing properties when compared to the commercial formulation (Murivenna oil). This study substantiates the wound healing and scar reduction potential of Tamanu oil bigels.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Lycopene is a compound of colored origin that shows strong antioxidant activity. The ability to neutralize free radicals by lycopene is the basis of its pro-health effect, including the ability to inhibit the development of many civilization diseases. Therefore, this study focuses on the importance of the antioxidant effect of lycopene in inhibiting the development of such diseases as cardiovascular diseases, diseases of the etiology of etiology, diseases within the nervous system.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSIL) but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3-month supplementation with 600 mg of ALA on antioxidant- and lipid status param-eters in 100 patients with LSIL were investigated in randomized placebo-controlled study. Obtained results were discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). Obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted with small but statistically significant increase of serum low density lipoprotein (LDL) and observed effect was significantly affected by the initial lipid status of participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Background: One of the main diseases of worldwide concern is non–insulin dependent Diabetes mellitus. 90-95% of patients with diabetes suffers from Type II diabetes, a metabolic diabetes whose prevalence is increasing in the world.Given the current prevalence of diabetes type II in society, research of natural compounds able to regulate glycaemia and insulin–resistance is nowadays covering importance, as alternative or co–adjuvant treatment to existing hypoglycaemic medicines. In pre–clinical steps of research, C. elegans is considered a promising in vivo model for the study of the molecular mechanism of glucose as part of anti–diabetic bioactivity.Most of the studies of insulin resistance with this in vivo model are carried out by using mutant strains such as daf-2 and the effects of the compounds are attributed a posteriori, after a physiological response of the worms rather than directly measuring preservation of activity inside the worm. Methods: The in vitro α-glucosidase inhibition of two oral formulations with Origanum vulgare extract before and after a simulated process of gastrointestinal digestion was evaluated. After confirming the in vitro activity, the α-glucosidase inhibition was tested in vivo through the new method proposed. Results: The crude extract showed an IC50 value similar to acarbose (positive control), before and after the gastrointestinal digestion. The encapsulated extract (111.86±1.25 µg/mL) did not present statistical differences with the positive control (110.10±1.15 µg/mL) after digestion. However, the powder formulation showed the highest hypoglycaemic activity (59.55±0.85 µg/mL).In vivo, the IC50 values showed similar profile than in vitro. Conclusion: A new simple and reliable method has been developed to determine pharmacological activities inside in vivo model C. elegans.The method has been evaluated with a hydroalcoholic extract of O. vulgare. The method is accurate and valid for the quantification of the inhibition of in vivo, allowing the direct attribution of this in vivo hypoglycaemic activity to the treatment. In addition, it opens the door to further research into in vitro pharmacological activities that require an in vivo counterpart.

Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

The osteoarthritis (OA), the main cause of disability, is a chronic condition that most frequently affects older adults. As the population ages, the cost of treatment is placing pressure on the healthcare budget. As a result, it is imperative to evaluate the medicines' cost-effectiveness and the influence they have on health resource allocation. Hence, our study aims to summarize the cost and outcome of utilizing glucosamine in OA treatment. Authentic databases like Medline, Cochrane, and Scopus were adopted for the identification process up until July 2023. Our primary inclusion criteria centered on the economic evaluation of Glucosamine in OA treatments with provided the incremental cost-effectiveness ratio (ICER) at least. The Quality of Health Economic Studies (QHES) instrument was applied to grade the quality of the studies. A total of 7 qualified studies were selected and discussed the cost-effectiveness of glucosamine with or without other formulations. All of them demonstrated that glucosamine was cost-effective. There was an in-creasement of QALY when incorporating Glucosamine into conventional care. Moreover, Crystalline Glucosamine Sulfate (pCGS) was more cost-effective than the Other Formulations of Glucosamine (OFG). In overall, utilizing pCGS was more beneficial than OFG in terms both of cost and quality of life.

Osteoarthritis (OA) is the degeneration of cartilage in joints that results in bones rubbing against each other, it causes uncomfortable symptoms such as pain, swelling, stiffness, and can lead to disability. It usually occurs in the elderly and causes a large medical burden. The aim of this study is to evaluate cost-effectiveness between the standard treatment for osteoarthritis and the standard treatment with added crystalline glucosamine sulfate at various stages. The Markov analysis modelling was applied to evaluate the effect of both adding glucosamine compared to standard treatment from a societal perspective during whole patients’ lifetimes. Data input was collected by review in previous studies. The outcome was measured in quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) from a societal perspective was ap-plied with 3%-discounted for all cost and outcome. One-way analysis via Tornado diagram was performed to investigate the change of factors in model. In general, the adding glucosamine into the standard treatment proved to be more cost-effectiveness compared to the standard treatment. Particularly, early stage adding glucosamine in the treatment was cost-effectiveness then post-stage adding glucosamine. The addition of supplementing crystalline glucosamine sulfate to whole regimen at any stage was cost-effectiveness at willingness-to-pay (WTP) threshold

Background: Best Possible Medication History (BPMH) collected by clinical pharmacists is crucial for effective medication review but, in Italy, it is often left to the nursing staff. This study aims to compare the quality and accuracy of a clinical pharmacist-documented BPMH with the current standard practice of ward staff-collected BPMH at an Italian perioperative surgical setting. Methods: A 20-week prospective observational non-profit study was conducted in a major University hospital. The study comprised a feasibility, an observational, and an interventional phase. During the feasibility phase, 10 items for obtaining a correct BPMH were identified. The control group consisted of retrospectively analyzed BPMHs collected by the ward staff during the observational phase, while interventions included BPMHs collected by the clinical pharmacist during the third phase. Omissions between the two groups were compared. Results: 14 (2%) omissions were found in the intervention group, compared with 400 (57.4%) found in the controls (p<0.05); data collection was more complete when collected by pharmacists compared to the current modalities (98.0% versus 42.6%; p<0.05). Conclusions: The involvement of a pharmacist significantly reduced the number of omissions in perioperative surgical-collected BPMHs. This intervention holds the potential to decrease the risk of medication errors associated with inaccurate or incomplete BPMHs prior to surgical hospitalization.

Lipid nanoparticles (LNPs) are promising carriers for constructing drug delivery systems (DDSs) in disease treatments. Previous studies have suggested that lipid composition and biophysical properties of LNPs can significantly impact their interaction with cells and tissues, allowing for the development of suitable LNPs for precise drug delivery. Our previous study proposed the concept and facile preparation of reconstituted lipid nanoparticles (rLNPs), which not only have the advantages of traditional LNPs but also contain the lipids of mother cell/tissue. In this study, we have found that brain-derived rLNPs (B-rLNPs) can have much better accumulation to the ischemic area of the ischemic stroke (IS) model than liver-derived rLNPs (L-rLNPs). This homing effect hopefully makes rLNPs a useful tool for developing highly accessible devices with homologous targeting ability for precise drug delivery.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

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.

Purpose: Oxidative stress is responsible for over seventy five diseases and other harmful cytological challenges including cancer, type 2 diabetes mellitus, lipid peroxidation, distortion of cell membrane integrity, shortening of telomerase among others. Antioxidant potency of any plant is a very positive remedy to the debilitating effects of prooxidants and oxidants. The study was aimed at investigating the antioxidant potency of methanol extract of Pentaclethra macrophylla stem bark- in vitro and in vivo. Methods: Different phytochemicals were determined using standard methods. Nitric oxide, 1, 1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity and ferric reducing/anti-radical power were used to investigate the in vitro antioxidant activity. Catalase assay, superoxide dismutase, malondialdehyde and glutathione peroxidase were used to determine the in vivo antioxidant efficacy using six groups of five rats. Results: The result showed various quantities of phytochemicals, including antioxidant phytochemicals-flavonoids, tannins and total phenolics. The in vitro assay showed that 250 μg/ml of extract had the highest percentage inhibition of DPPH radical (93.93%). The 125 μg/ml had the highest scavenging activity of nitric oxide radical (49.47%) while 250μg/ml showed the least with 41.73%. Other methods showed various degrees of activity. The in vivo antioxidant showed that the principal mechanism of antioxidant activity is by modulating the iron-dependent catalase activity. Conclusion: Pentaclethra macrophylla has both in vitro and in vivo antioxidant activities and therefore is useful in ameliorating the debilitating effects of oxidants.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data is available on CYP2C9*2 and CYP2C9*3 alleles in Pakistani population. In Pakistan pharmacogenetics which examines the relationship between genetic factors and drug response, are in the early stages of development. We for the first time investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycemia in diabetic patients who were receiving the sulfonylurea medications. A total of n=400 individuals of Pashtun ethnicity were recruited from ten different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n=200) and the control group (n=200). The case group consisted of individuals with Type 2 Diabetes Mellitus (T2DM) who were receiving sulfonylurea medications and experience hypoglycaemia with it whereas the control group included individuals with T2DM who were receiving sulfonylurea medication but did not experience sulfonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at centre of genomics Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low activity allele) was more frequent in the diabetic patients with sulphonylurea-induced hypoglycaemia (SIH) compared to the control group (17.5% vs. 6.0%, p=0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to control group (10% vs. 6% with P=0.036), same was true for genotype CYP2C9*2/*2 (7% vs. 3.5 % with P=0.028). Logistic regression analysis evident potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such age, weight, sex, daily dose of sulphonylurea and triglyceride level the association between the CYP2C9*2 allele and hypoglycemia remains consistent. Confounding factors played no role in SIH because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea and trigyleride levels. Our study suggests that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic make-up.

Granulomatous mastitis is a benign disease with a clinical presentation similar to that of breast cancer, and is most commonly observed in women of childbearing age. Although it has been suggested that autoimmune diseases are involved in its pathogenesis, no specific treatments have been established. The occurrence of this disease during pregnancy has rarely been reported. Our patient was a 37-year-old woman. She was pregnant and manifested a dichorionic, diamniotic placenta. At 24 weeks of gestation, the patient experienced a sensation of hardness in her left breast. Mastitis was suspected, and she was treated with cephem antibiotics. Simultaneously, she was diagnosed with erythema nodosum in the extremities. As her symptoms did not improve, an incisional drainage was performed. Bacterial cultures were obtained at 31 weeks of gestation, and Corynebacterium kroppenstedtii was detected. An elective cesarean section was performed at 37 weeks of gestation, and the baby was delivered safely. After delivery, a needle biopsy was performed, and the patient was diagnosed with granulomatous mastitis. She was completely cured with prednisolone after weaning. In this case, the patient's condition was maintained through incision and drainage; and antibiotic, anti-inflammatory, and analgesic drugs during pregnancy. This approach was chosen, taking into consideration the potential side effects of steroids. After delivery, breastfeeding and steroidal therapy proved to be effective in treating the condition.

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO2 laser for the manufacturing of carvedilol personalised dos-age forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.125, 6.25 and 12.5 mg. The tuning of the SLS processing parameter laser intensity, improved printability and impacted the tablet hardness, friability, CVD dissolution rate, and the total amount of drug re-leased. Physicochemical characterization showed the presence of CVD in the amorphous state. X-ray micro-CT analysis demonstrated that the applied CO2 intensity affected the total tablet po-rosity, which was reduced with increased laser intensity. The study demonstrated that SLS is a suitable technology for the development of personalised medicines that meet the required specifications and patient needs.

The lactoperoxidase (LPO) system shows promise in the prevention of dental caries, a common chronic disease. This system has antimicrobial properties and is part of the non-specific antimicrobial immune system. Understanding the efficacy of the LPO system in the fight against biofilms could provide information on alternative strategies for the prevention and treatment of caries. In this study, the enzymatic system was modified using four different (pseudo)halide substrates (thiocyanate, thiocyanate-iodide mixture, selenocyanate, and iodide). The study evaluated the effects of such modifications on the ability of Streptococcus mutans to form a biofilm, the synthesis of insoluble polysaccharides, the synthesis of lactate, the consumption of glucose and sucrose, the concentrations of intracellular NAD+ and NADH and the efficiency of transmembrane glucose transport by phosphoenolpuryvate PEP-carbohydrate phosphotransferase (PTS). The results showed that the LPO-iodide system had the strongest inhibitory effect on biofilm growth and lactate synthesis (complete inhibition). This was associated with an increase in the NAD+/NADH ratio and an inhibition of glucose PTS activity. The LPO-selenocyanate system showed a moderate inhibitory effect on biofilm biomass growth and lactate synthesis. The other systems showed relatively small inhibition of lactate synthesis and glucose PTS but no effect on the growth of biofilm biomass. This study provides a basis for further research on the use of alternative substrates of the LPO system, particularly the LPO-iodide system, in the prevention and control of biofilm-related diseases.

Prevalence of antimicrobial-resistant bacteria has become a major challenge worldwide. Methicillin-resistant Staphylococcus aureus (MRSA)—a leading cause of infections—forms biofilms on polymeric medical devices and implants, increasing their resistance to antibiotics. Antibiotic administration before biofilm formation is crucial. Raman spectroscopy was used to assess MRSA biofilm development on solid culture media from 0 to 48 h. Biofilm formation was monitored by measuring DNA/RNA-associated Raman peaks and protein/lipid-associated peaks. The search for an antimicrobial agent against MRSA biofilm revealed that Eugenol was a promising candidate as it showed significant potential for breaking down the biofilm. Eugenol was applied at different times to test the optimal time for inhibiting MRSA biofilms, and the Raman spectrum showed that the first 5 h of biofilm formation was the most antibiotic-sensitive time. This study investigated the performance of Raman spectroscopy coupled with Principal Component Analysis (PCA) to identify planktonic bacteria from biofilm conglomerates. Raman analysis, microscopic observation, and quantification of the biofilm growth curve indicated early adhesion from 5 to 10 h of incubation time. Therefore, Raman spectroscopy can help in monitoring biofilm formation on a solid culture medium and performing rapid antibiofilm assessments with new antibiotics during the early stages of the procedure.

The COVID-19 pandemic has expanded globally and caused serious consequence in both health system and the economy. MPV is one of two oral antivirals for COVID-19 with mild-to-moderate symptoms that have received FDA approval so far. This study aims to evaluate the cost-utility of using MPV in COVID-19 treatment. To compare the utility costs of MPV and non-MPV treatments for COVID-19 patients, we used a decision tree model. Data on clinical efficacy, cost, and quality of life were gathered from previous studies. The incremental effective cost ratio (ICER) calculated based on costs incurred and quality-adjusted life years (QALY), was considered as primary out-come. The total cost of MPV treatment and not using MPV was 15,362,516 VND (618 USD) and 15,771,262 VND (634 USD), respectively. The estimated QALY with using-MPV was 28.33, while without MPV was 19.72. The ICER was dominant, resulting in savings of 47,453 VND/QALY (1.9 USD). MPV is a cost-effective medication used to treat COVID-19. In mild-to-moderate COVID-19 patients, MPV considerably lowers costs and improves quality of life. However, several clinical factors of the drug still need to be taken into account.

Cancer is the most feared disease, with more than 1.6 million cases each year. Cancer can start almost anywhere in the human body, from the uncontrollable growth and multiplication of damaged cells. Cancerous tumors can spread into the human body (a process called metastasis) as a solid form usually, but the cancers of blood generally do not. Cancer treatment includes chemotherapy, surgery and radiations. In this article we will address inorganic compounds as a source of treatment, diagnosis, carriers of active substances.

The ameliorative effect ethanolic extract of M. oleifera (MO) leaves in combination of curcumin against seizures, cognitive impairment & oxidative stress PTZ-induced kindled rats. Molecular docking was performed to predict the potential phytochemical of MO and curcumin against Epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250, 500mg/kg, orally), curcumin (200 and 300 mg/kg, orally), valproic acid used as standards (100mg/kg) and combined effect of MOEE (250mg/kg) and curcumin (200mg/kg) at low dose, on pentylenetetrazole (PTZ)-induced kindling. For the development of kindling the individual Wistar rats (Male) were injected pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular Docking has been done by AutoDock4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of Human Glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and MOEE showed dose-dependent effect. The combined effects of leaves of MOEE & curcumin significantly improved the seizure score and decreased the number of myo-clonic jerks in compare with standard dose of valproic acid. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with MOEE & curcumin. Glutathione reductase (GR) is an enzyme, which plays key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift the antioxidant property, which leads to the inhibition of ROS induced cell death in brain. The combination of ethanolic extract of M. oleifera (MOEE) leaves and curcumin have shown better result than any other combination for antiepileptic effect by virtue of antioxidant effects. As per docking study showed that the chloro-genic acid and quercetin is treated with the combination of curcumin can be much more potential.

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. For this, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epider-mal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), Serine/threonine-protein kinase mTOR (mTOR) and Poly [ADP-ribose] polymerase-1 (PARP1). Then, mapped single nucleotide polymorphisms and designed target mutations, and performed molecular docking with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Background: The clinical outcomes of antiretroviral drugs may be modified by drug interactions; thus, it is important to update the drug interactions in people living with HIV. Aim: To update clinically relevant drug interactions in people living with HIV on antiretroviral therapy. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. The clinical relevance of drug interaction was grouped into 5 levels according to gravity and probability of occurrence. Results: 361 articles were identified and 148 were included, which allowed the identification of 894 drug interaction pairs. Among these 894 drug pairs, 355 have not been identified previously; and 89 (25.1%) and 72 (20.2%) were of levels 1 and 2, respectively. In addition, for 197 (55.5%) pairs the mechanism was pharmacokinetic. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) with 91 (25.6%) and 76 (21.4%) pairs, respectively were more frequent. Conclusions: In people living with HIV on antiretroviral therapy, we identify 355 new drug interaction pairs, of them 161 (45.3%) are assessed as levels 1 and 2 and thus, clinically relevant; a figure that is lower compared to 2014-2107 update. The pharmacokinetic mechanism is the most frequently identified. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) are the antiretroviral groups with the highest number of clinically relevant drug interactions.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency i.e. 5.13±0.10% and 82.36±4.01%, respectively. SC PLGA NPs showed a spherical morphology on an average size (134.8±4.61nm), PDI: 0.277±0.004, and −25.3±1.03mV zeta-potential is suitable for oral delivery. Development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameters examinations with 1.219-minutes RT, MS (162.00/73.10), and a total run-time was 2.0-minutes. 1.0–1000.0ng/mL was a linear-range with inter & intra-day accuracy (92.55–99.40%) followed by precision (1.88–4.23%). SC PLGA NPs oral bioavailability was significantly higher (**p<0.01) as compared to SC-S treated groups (iv & oral). We found that the antimicrobial activity of SC PLGA NPs was more effective than pure S-Allyl-L-Cysteine with significant results (p<0.01) as compared to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties which can be helpful for oral administration. On the basis of our observations, SC PLGA NPs suggested the highest potential for the improvement of oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

Oral and parenteral delivery of first-line anticonvulsant Valproic cid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in brain. GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in human. HSPiP software predicted excipients with maximum possible miscibility of the drug. Based on GastroPlus and HSPiP program, various excipients were screened for experimental solubility study and prepared cationic nanoemulsions and respective gels for nasal to brain delivery. These were characterised for size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Result showed that in-vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively from both tablets (IR and SR) at 8 h using GastroPlus. The drug access to the portal vein was relatively predicted high in IR (115 mg) as compared to SR (82.6 mg). Plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime site of drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested suitable selection of excipients. The program recommended for nasal to brain delivery of the drug using cationic mucoadhesive product. The optimized stable CVE6 was associated with optimal size (113 nm), low PDI (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7 %w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. Penetration study executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6 which may be attributed to electrostatic interaction between mucosal membrane and nanoglobules. Thus, cationic nanoemulsion and respective mucoadhesive gel are promising strategy for delivery of VA to brain through intransal administration for the treatment of seizure and convulsion.

Knee osteoarthritis is the most popular type of osteoarthritis that causes extreme pain in elderly. Currently there is no cure for osteoarthritis. To lessen clinical symptoms, glucosamine was suggested. The primary goal of our study is to evaluate the efficacy and safety of glucosamine from recent studies. Electronic databases such as PubMed, Scopus, Cochrane were used to assess RCT. From the beginning through March 2023, the papers were checked, and if they fulfilled the inclusion criteria, they were then examined. WOMAC and VAS scales were considered as main outcome measure. A total of 15 studies were selected. Global pain was significantly decreased in comparison to placebo, as measured by the VAS index, with an overall effect size SMD of -7.41 ([95% CI] 14.31, 0.51). The WOMAC scale confirmed that pain, stiffness, and physical function had improved, however the effects were insufficient. A statistical update also revealed that there were no reports of serious medication interactions or significant adverse events. To summarize, glucosamine is more effective than a placebo at reducing pain in knee osteoarthritis patients. In long-term treatment, oral glucosamine sulfate 1500 mg/day is believed to be well tolerated.

Recently, 3D printing techniques gained much attention in solid dosage form production. Even though the methods are increasingly studied, there are still many challenges in establishing an accurate content of active ingredients in the final products. In the present study, new experimental design techniques and statistical software were developed to identify and optimize a formula to predict the mass of the tablet to be 3D printed before it actually is. The first step was to develop a virtual 3D object in the FreeCad Software, then, using a CURA slicer software, the G-code Format was obtained. The tablets were printed using a Cartesian 3D printer based on the generated data. Finally, adapting the object sequencing mode, a predicted drug mass value was obtained. As expected, the oblong tablet's scaling directly influences its mass. The software generates a correlation coefficient (r) of 0.84, confirming the directly proportional relationship between scaling and tablet weight. However, the r values progressively decreased, indicating a poor correlation between tablet weight and other factors: infill density percent (r = 0.403) and wall thickness (r = 0.185). After repeating the 3D printing with the values ​​suggested by the software, tablets with a practical value of 1066 mg were obtained. Considering that the confidence interval calculated is [834.95—1165.05] and the experimental value is 1066 mg, it can be certified that the proposed model is valid.

: We evaluated the pharmaceutical properties of levofloxacin (LV) in the form of an orally disintegrating tablet (LVODT) to find a new usefulness of low frequency (LF) Raman spectroscopy. LVODT contained dispersed granules with diameters in the order of several hundred micrometers, which were composed of the active pharmaceutical ingredient (API), as confirmed by infrared (IR) microspectroscopy. On the contrary, the API and inactive pharmaceutical ingredients (non-APIs) were homogeneously distributed in LV tablet (LVT) formulations. Microscopic IR spectroscopy and thermal analyses showed that LVODT and LVT contained the API in different crystalline forms or environment around the API each other. Furthermore, powder X-ray diffraction showed that LVT contained a hemihydrate of the API, while LVODT showed a partial transition to the monohydrate form. This result was confirmed by microscopic LF Raman spectroscopy. Moreover, this method confirmed the presence of thin layers coating the outer edges of the granules that contained the API. Spectra obtained from these thin layers indicated the presence of titanium dioxide, suggesting that the layers coexisted with a polymer that masks the bitterness of API. The microscopic LF Raman spectroscopy results in this study indicated new applications of this method in pharmaceutical science.

Background: Currently, limited number of therapeutic options are available to treat Diabetes mellitus, and to find a potential candidate, laboratory work takes time and also needs animal studies. So, the aim of this study was to determine the efficacy of some natural phytocompounds with the aid of molecular docking, bioinformatics and in silico drug design approaches. Method: Two proteins (Human CYP3A4 linked to metformin and Human dipeptidyl peptidase-IV) were selected and molecular docking studies were conducted using Pymol, AutoDock Vina, PyRx, and Discovery Studio. Different important pharmacokinetic parameters like ADME and toxicity data were obtained from online databases SwissADME and pkCSM program. Results: It was found that human dipeptidyl peptidase-IV (PDB ID: 4A5S) has exhibited a maximal affinity of -9.7 Kcal/mol for bryonolic acid and hesperidin, but only -6.7 kcal/mol for metformin hydrochloride. Similarly, the highest affinity of hesperidin for human CYP3A4 bound to metformin (PDB ID: 5G5J) is -10.7 Kcal/mol compared to metformin hydrochlor (-6.3 Kcal/mol). Besides, all the compounds have been documented outstanding ADMET profile, and accepted by drug-likeness or Lipinski rule. Conclusions: The present study suggested that these compounds can be further investigated in vitro and in vivo to establish them as lead compounds against Diabetes mellitus..

Essential oils (EOs) have gained economic importance due to their biological activities, and increasing amounts are demanded everywhere. However, substantial differences between the same essential oil samples from different suppliers are reported due to numerous companies involved in EOs production and the continuous development of online sales. The present study investigates the antibacterial and antibiofilm activities of 2-4 samples of five commercially available essential oils (Oregano, Eucalyptus, Rosemary, Clove, and Peppermint oils) from different manufacturers. Their effects were evaluated in vitro on Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa). The antibacterial efficacy (ABE%) and antibiofilm efficacy (ABfE%) were determined spectrophotometrically at 562 and 570 nm using microplate cultivation techniques. The essential oils' calculated parameters were compared with those of three standard broad-spectrum antibiotics: Amoxicillin/Clavulanic acid (AMC), Gentamycin (GEN), and Streptomycin (STR), active on tested bacteria. The results showed that at the first dilution (D1 = 2.5 mg/mL), all essential oils (EOs) exhibited antibacterial activity against Gram-positive and Gram-negative bacteria. On S. aureus and E. coli, EOs had considerable antibacterial effects (ABE = 79.70—92.80%, respectively, 71.30 ‒ 94.00%). The highest antibacterial effects of commercially available EOs were against P. aeruginosa because all exhibited a significant antibiofilm activity. Their antibiofilm efficacy intensively decreased on E. coli and S. aureus. Generally, the samples with different manufacturers of the same EO showed similar effects. Only Clove and Peppermint oils samples displayed a higher variability associated with active metabolites' different contents, maybe due to various zones of harvesting raw material, numerous technologies involved in EOs obtaining processes, and complex interactions between components.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

The human respiratory syncytial virus (hRSV) poses a serious risk to global public health and is a significant cause of severe lower respiratory infections. There are currently only a few therapies available to treat RSV infections, as well as no RSV vaccinations. Therefore, there is an urgent demand for clinically feasible, safe, and affordable RSV prevention and treatment alternatives. In this study, an ion-activated in situ gel comprising broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) for antiviral action on RSV was developed. In this content, mechanical properties, sprayability, drug content, pH, ex vivo mucoadhesive strength, in vitro drug release pattern, and stability were all examined. Rheological properties were also tested by utilizing in vitro gelation capacity and rheological synergism tests. Finally, the optimized in situ gel's cytotoxic and antiviral activities on RSV cultured in human laryngeal epidermoid carcinoma (HEP-2) cell line were evaluated. In conclusion, the optimized in situ gel prepared with a combination of 0.5%w/w gellan gum and 0.5%w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between T0 and T14: 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53), mechanical characteristics (adhesiveness: 0.300 mJ ± 0.05), ex vivo bioadhesion force (19.67 g ± 1.90), drug content uniformity (RSD%: 0.494), and sustained drug release over period of 168 h (101.57% ± 0.53). The antiviral activity test results showed that the optimized in situ gel had strong anti-HRSV activity (EC50 simultaneous = 0.05 µg/ml, SI = 306; EC50 preinfection = 0.154 µg/ml, SI= 100) which was significantly higher than that of ribavirin (EC50 =4.189 µg/ml; SI= 28) used as a positive control against hRSV. In conclusion, this research has demonstrated the formulation of an effective antiviral nasal spray that has the ability to possess both prophylactic and virucidal activity.

The aim of the current study was to develop and evaluate the therapeutic potential of apocynin (APO) loaded pH-sensitive nanoparticles (NPs) based transdermal hydrogel for management of rheumatoid arthritis (RA). Slightly modified nanoprecipitation technique was used for preparation of polymeric nanoparticles. Optimization was done through design expert software. Optimized APO-NPs were loaded into carbopol-934 based hydrogel as final dosage form and further studied for physicochemical properties. Optimized APO-NPs formulation had a minimum particle size 63.44 nm, polydisperibility index 0.161, and zeta potential -15mV with a maximum encapsulation efficiency of 89%. In-vitro and ex-vivo studies of APO-NPs based hydrogel was performed at pH 5.5 (pH of normal skin) and 6.8 (pH of inflammed joint) showed a pH-responsive sustained drug release and increased penetration in comparison to free APO based hydrogel. The stability studies of APO-NPs based hydrogel were done to strengthen the potential use of the prepared formulation through transdermal route. Assessment and therapeutic efficacy of the prepared pH-sensitive nanocarriers system was evaluated in chronic inflammatory RA mice model. Parameters associated with chronic inflammation were investigated including behavioral changes and histopathological, and radiological x-rays images of joints of mice paws. In-vivo study depicts improvement in behavioral parameter, decline in synovial hyperplasia and bone structure restoration. In conclusion, APO loaded pH-sensitive NPs based transdermal is a promising carrier system that can effectively manage RA.

The present study aims at valorizing Moroccan Henna (Lawsonia inermis) by developing healing formulations for cosmetic and therapeutic uses. For such a goal, the plant was collected from three locations in Southeastern Morocco (Alnif, Tafraoute Sidi Ali and Tazarine). Phytochemical anal-yses of aqueous extracts of Henna leaves was performed by determining phenolic compounds contents, flavonoids and tannins in the extracts. Then, specific formulations were prepared using aqueous extracts of L. inermis to assess their in vivo wound healing potential in Swiss Albino mice as animal model. Results disclosed that phenolic compound contents (13.48%), flavonoids (9.25%) and tannins (2.57%) are higher in Henna leaf extracts from Alnif, while Tazarine Henna aqueous extract was found to be richer in saponins (0.32%). Exclusion chromatographic analysis on Se-phadex G50 gel corroborates the obtained results and shows that Lawsone levels (Henna coloring agent) are higher in Henna collected from Alnif. Aqueous Henna leaf extracts, at a dose of 10% in petroleum jelly, have been tested for their ability to heal induced burns in mice. Healing moni-toring, carried out with Henna extracts on mice batches and those of two control batches (Mice batch treated with petroleum jelly alone and batch treated with petroleum jelly containing 1% flamazine), showed a great reduction in burnt surface with an accentuated contraction percentage (CP) and complete re-epithelialization duration (CRD) at 21 days in the three studied Henna-based formulations. These findings suggest the interest of potential development of Henna-based for-mulations, as source of phenolic compounds, for further dermatological, cosmetic and therapeutic applications.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Inflammation is the response of the immune system to infection and injury, with complex interactions with the body, tissues and cells, and plays an important role in the initiation and progression of many diseases such as cancer and cardiovascular disease. Traditional excipients functioning as drug delivery systems can reduce the side effects of systemic distribution of inflammatory drugs. Oil phase, a common excipient in nanoemulsions (NEs), has the advantages of assisting the formation of emulsions, loading lipophilic drugs, thermodynamic stability, wide sources, low price and easy availability. In particular, some of them, like linolenic acid and medium chain triglyceride (MCT), also function as inhibitors of systemic inflammation marker and vascular inflammation marker. However, the influences of different oil phases on the construction of NEs and their distribution in vivo have not been fully investigated. Herein, Tween 80 and ethyl alcohol were screened out as emulsifiers and co-emulsifiers, and three different oil phases used in clinical practice widely, including MCT, oleic acid (OA), and ethyl oleate (EO), were selected as the oil phase to prepare NEs delivery platform. Three NEs had consistent size, potential, morphology, excellent stability and mitochondrial localization function. Importantly, they exhibited superior cellular uptake capacity in inflammatory-injuried human umbilical vein endothelial cells and significantly targeted the brain, lung, heart and thoracic aorta in the lipopolysaccharide-induced mouse and zebrafish larvae inflammation models. Meanwhile, the fluorescence intensities of three NEs were different in these organs, suggesting that their differential enrichment might provide alternative delivery platform for disease treatment in the corresponding organs.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

Due to their increased surface area, extent of swelling and active substance loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in the scientific and industrial areas. Especially, customized design and implementation of non-toxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels have been outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications have been discussed, with a particular emphasis on applications for the delivery of drugs and biomolecules.

Antibiotics have become a widely used drug classes worldwide. Its indiscriminate use in the clini-cal-hospital environment ended up causing antibiotic-resistance genes. Pharmaceutical technology is an essential ally for new formulation development in the antibacterial field. Cyclodextrins (CDs) are ap-proaches that can potentially improve the effectiveness of antibacterial drugs. Thus, this study aimed to review experimental models using CDs as inclusion complexes to improve antibacterial drugs’ physi-cochemical characteristics and biological activities. The review was carried out using the three online journals database PubMed, Scopus, and Embase, limited to Medical Subjects Headings Index. The search protocol was registered in the Open Science Framework database. The following terms and their com-binations were used: cyclodextrins and antibacterial agents in title or abstract, and a total of 1580 studies were identified in a period up to October 2022. Finally, 27 articles were selected for discussion in this review. The biological results reveal that the antibacterial effect of the compounds, complexed with CDs, was extensively improved when compared to the free drugs. CDs can improve the therapeutic effects of antibiotics, already existing on the market, natural products, and synthetic molecules. Therefore, these inclusion complexes using CDs increase the new pharmaceutical products development for clinical ap-plication.

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.

The liver performs a fundamental role in the regulation of diverse physiological processes. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, offer complete protection to the organ, or aid in regenerating hepatic cells. Thus, it is necessary to identify alternative plant-origin pharmaceuticals more effective and less toxic for the treatment of hepatic diseases. The aim of this research was to establish the chemical composition of the American cranberry (Oxycoccus macrocarpus) leaves extract and its aminoacids preparations as well as their hepatoprotective activity. 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 2 catechins, and 3 hydroxycinnamic acids) and main amino acids (valine, arginine, glycine, histidine, aspartic acid, and taurine) were identified and quantified in the American cranberry (O. macrocarpus) leaves extract and its 7 aminoacids preparations. The therapeutic and prophylactic consumption of the American cranberry leaves extracts led to a decrease in the intensity of the lipid peroxidation process compared to the control pathology group in the experiment of acute toxic damage to the liver by tetrachloromethane on rats. The most pronounced hepatoprotective activity was established for the American cranberry leaves extracts’ preparations with arginine and valine.

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts), the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoportegerin, osterix, RANKL, Runx2) and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others presented a beneficial and stimulating effect in the bone regeneration process due to pro-estrogenic activity, antioxidant and anti-inflammatory effects and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone related pathologies envisaged by incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

This study aimed to develop chitosan-based apigenin spray dried solid dispersion using 1:1,1:1.5,1:2 w/w ratios. The results of process yield and drug assay were found to be (87.5%, 94.2%, and 95.86%), (95.2 ±1.34%), (99.5 ±0.85%), and (97.6 ±2.42%), respectively, for AC1, AC2, and AC3. Flow properties indicate the free flow of powders. FTIR revealed compatibility among chitosan and apigenin, and DSC and XRD showed prepared solid dispersion was on a molecular level and available in amorphous. In contrast, SEM images reflect irregular block and near-spherical shape elongated particles in the selected AC2. The antimicrobial examination reflects that AC2 was more effective against Gram-positive, negative, and fungal strains. AC2 SDSDs has more anti-oxidant property compared to pure flavonoid (AGN). Anti-proliferative activity against A549 lung cancer cell lines showed better anti-cancer activity by AC2 SDSDs. The selected AC2 SDSD filled in a 3D shell pill and further characterized for 3D shell pill for dissolution profiles and stability studies. The product has sustained release and similar release profiles after three months of storage. The findings suggest that the AC2 SDSDs may be a promising candidate for further development as a 3D printed drug delivery system for treating multiple disease conditions using model flavonoid- apigenin.

Background: The AWaRe tool was set up by the World Health Organization (WHO) to promote the rational use of antimicrobials. Indeed, this tool classifies antibiotics into four groups, Access, Watch, Reserve and not-recommended antibiotics. In Republic Democratic of Congo, data on antibiotic dispensing (prescribing) by health professionals according to the AWaRe classification are scarce. In this research work, we aimed to explore antibiotic dispensing pattern from health professionals according to the WHO AWaRe classification to strengthen the national antimicrobial resistance plan. Methods: For this purpose, a survey was conducted from July to December 2022 in the district of Tshangu in Kinshasa. From randomly selected drugstores, drug-sellers were interviewed and randomly selected customers attending those drugstores were included in the study for medical prescriptions collection. The prescribed antibiotics were classified into the Access, Watch, Reserve and not recommended antibiotics group and by antibiotics number by prescription among pharmacies surveyed. Results: Of 400 medical prescriptions collected, 301 (75.25%) contained antibiotics. Of 301 prescriptions containing antibiotics, 164 (164/301; 54.5%) contained one antibiotic, 117 (117/301; 38.9%) two antibiotics, 15 (15/301; 5%) three antibiotics and 5 (5/301; 1.6%) 4 antibiotics. Out of the total of 463 antibiotics prescribed, 169 (169/463; 36.5%) were from the Access group, 200 (200/463; 43.2%) from the Watch group and 94 (94/463; 20.3%) from not recommended antibiotics group, respectively. Based on the anatomical, therapeutic and chemical (ATC) classification, it can be seen that third generation cephalosporins contained 34.33% of the prescribed antibiotics, followed by penicillins 17.17%, macrolides 7.63%, aminoglycosides 7. 36% and Imidazoles 7.36%, thus accounting approximately for 74% of the classes of antibiotics prescribed. Of the 463 antibiotics prescribed, the most frequently prescribed antibiotics were Ceftriaxone (21.38%), Amoxicillin (11.01%), Gentamycin (5.61%), Amoxicillin-clavulanic acid (5 .61%), Azithromycin (4.97%) and Metronidazole (4.75%), thus accounting for approximately 54% of all antibiotics prescribed. Conclusion: These results highlight the importance of strict implementation of the national plan to combat antimicrobial resistance and the need to train health workers in the correct application of the WHO AWaRe classification.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

Artificial Intelligence (AI) is a breakthrough technology that has been widely applied in many fields and its use in pharmacy is also gaining increasing attentions. Recently, ChatGPT, a newly developed virtual assistant and large language model, is showing strong ability in writing, which makes it a potential tool for review writing. Here in our study, we employ the public available ChatGPT and try to instruct it to generate a mini review on the topic of “lipid-based drug delivery systems” by conversation. Our results showed that ChatGPT can give reasonable outline for this topic and give seemingly sentences with concluding wording, which can give useful information to the readers. However, the accuracy and consistence of the review are not fully guaranteed and there is lack of reliable citations. Therefore, it is concluded that ChatGPT can only give general knowledge on the selected topic, but not capable of giving in-depth discussion. The generated review article can be a useful but occasionally unprecise electronic encyclopedia instead of rigorous scientific literature, which can give benefit for pharmaceutical education and interchange to some extent.

Core-shell particles are heterogenous micro- or nanoparticles with solid, liquid or gas core encapsulated by a protective solid shell. The unique composition of core and shell materials imparts smart properties to the particles. Core-shell particles are gaining increasing attention as tuneable and versatile carriers for pharmaceutical and biomedical applications including targeted drug delivery, controlled drug release, and biosensing. This review first provides an overview of fabrication methods for core-shell particles, followed by a brief discussion on their application and a detailed analysis on manipulation including assembly, sorting, and triggered release. We compile current methodologies employed for manipulation of core-shell particles and demonstrate how existing methods of assembly and sorting micro/nanospheres can be adopted or modified for core-shell particles. Various triggered release approaches for diagnostics and drug delivery are also discussed in detail.

Background. The European Centre for Disease Prevention and Control describes the community pharmacist as gatekeeper to the quality of antibiotic use. The pharmacist has the responsibility to guard safe and effective antibiotic use; however, little is known about how this is implemented in practice. Aims. To assess the feasibility of a method to audit the quality of antibiotic dispensing in community pharmacy practice and to explore antibiotic dispensing practices in Greece, Lithuania, Poland, and Spain. Methods. The Audit Project Odense methodology to audit antibiotic dispensing practice was adapted for use in community pharmacy practice. Community pharmacists registered antibiotic dispensing on a specifically developed registration chart and were asked to provide feedback on the registration method. Results. Altogether twenty pharmacists were recruited in four countries. They registered a total of 409 dispenses of oral antibiotics. Generally, pharmacists were positive about the feasibility of implementing the registration chart in practice. The frequency of checking for allergies, contraindications and interactions differed largely between the four countries. Pharmacists provided little advice to patients. The pharmacists rarely contacted prescribers. Conclusion. This tool seems to make it possible to get a useful picture of antibiotic dispensing patterns in community pharmacies. Dispensing practice does not seem to correspond with EU guidelines according to these preliminary results.

(1) Background: Rational use of medicines (RUM) and their assessment is important to ensure optimal use of resources and patient care in hospitals. These assessments are essential to identifying practice gaps for quality improvement. (2) Methods: Assessment of adherence to WHO/ International Network for Rational Use of Drugs core prescribing indicators among out-patients in 2021 was conducted at the University Hospital of the Kwame Nkrumah University of Science and Technology in the Ashanti region of Ghana. We reviewed electronic medical records (EMR) of 110,280 patient encounters in the year which resulted in 336,087 medicines prescribed. (3) Results: The average number of medicines prescribed per encounter was 3 with generics being prescribed in 76% of prescriptions. Injections were prescribed in 7% of encounters while 90% of medicines were from Ghana’s Essential Medicines List 2017. (4) Conclusions: With the exception of patient encounters with injections, all prescribing indicators assessed in this study did not meet WHO optimum levels providing targets for quality improvement in RUM. Implementing prescribing guides and policies, regular audits and feedback as well as continuous professional development training may help to improve prescribing practices in the hospital.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

Objective tools to track medication adherence are lacking. A tool to monitor pill intake that can be implemented in mHealth apps without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the circular Hough transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills need to be further improved, in particular for the detection of pills with non-oval shapes.

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are underactive debate. However, in our opinion it is becoming increasingly likely that electrophiles can rewire cellular signaling processes at endogenous levels. Attention is turning more to understanding how nuanced electrophile signaling in cells is. In this perspective, we describe recent work from our laboratory that has started to inform on different levels of context-specific regulation of proteins by electrophiles. We discuss the relevance of these data to the field, and to the broader application of electrophile signaling to precision medicine development, beyond the traditional views of their pleiotropic cytotoxic roles.

Molecular Dynamics (MD) simulations model motion of molecules in atomistic detail and aid in drug design. While simulations on large systems may require several days to complete, analysis of terabytes of data generated in the process could also be time consuming. Recent studies captured exciting and dramatic drug-receptor interactions under cell-like complex conditions. Such advances make simulations of biomolecular interactions more realistic, insightful, and informative and have potential to make drug design more realistic. However, currently available resources and techniques do not provide, in reasonable time, a comprehensive understanding of events seen in simulations. We demonstrate that big data approach results in significant speedups, and provides rapid insights into simulations performed. Advancing this improvement, we propose a scalable, self-tuning, and responsive framework based on Cloud-infrastructure to accomplish the best possible MD studies with given priorities and within available resources.

Agaricus bisporus is belonging to family agaricaceae, which is widely acceptable and mostly cultivated among the all mushrooms. It has great nutritional values and it is rich in proteins, vitamins, carbohydrates, fibers, minerals and amino acids. It is effective in antimicrobial, anticancer, antidiabetic, antihypercholesterolemic, antihypertensive, hepatoprotective and antioxidant activities. As it is effective in anticancer property, we check the effects of chemical constituents of Agaricus Bisporus on DNA damaging protein which results its activity PARP inhibiting or vise-versa. We choose the molecular docking technique to check the effects of different chemical constituents of Agaricus Bisporus on DNA damaging protein. For that different PARP inhibitory drugs taken as the standard. We perform the molecular docking of the chemical constituents of Agaricus Bisporus, using 4UND protein with the help of PyRx software and BIOVIA Discovery studio software. Along with that PARP inhibitor drugs also run against the same protein. The results of molecular docking shows the some of the constituents of Agaricus Bisporus has better binding affinity than the standard taken PARP inhibitor drugs. The ergosterol shows the better binding affinity than the niraparib and rucaparib on the same proteins. On other hands the naringenin, quercetin, anthocyanin, folate and myricetin shows the better results than the rucaparib. That means the ergosterol shows the better results as PARP inhibitor than the niraparib and rucaparib.

Oyster mushroom( Pleurotus ostreatus) is belong to the group of healthy foods, as they contain high levels of proteins, vitamins and different classes of compounds, it is discovered that oyster mushrooms could play a key role in maintaining good health. Oyster mushroom (Pleurotus sp.) Class Basidiomycetes and Family Agaricaceae are widely known as ‘dhingri’ in India. Pleurotus Ostreatus have several medicinal properties including ; anti-arthritic , antitumor, immune modulatory , antioxidant, anticancer, anti-inflammatory, antigenotoxic, hypo-cholesterolaemic, antihyperglycaemic antihypertensive, antiplatelet aggregating, antiviral and antimicrobial activities.. In this paper studied that effects of chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein which analyzed its activity of PARP inhibiting or vice – versa.For this analysis we choose the molecular docking technique to check the effects of different chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein and compare their results to PARP inhibitory drugs which taken as standard . We perform the molecular docking in between chemical constituents of oyster mushroom(Pleurotus sp.) and 4UND protein compare to performance of molecular docking in between standard PARP inhibitory drugs and 4UND protein with the help of PyRx and BIOVIA Discovery studio software.The analysis of molecular docking shows that some chemical constituents of oyster mushroom(Pleurotus sp.) having more binding affinity than standard PARP inhibitory drugs .The Rutin shows better binding affinity than PARP inhibitory drugs on the same protein.

Drug repositioning (also called drug repurposing) is a strategy for identifying new therapeutic targets for existing drugs. This approach is of great importance in pharmacology as it is a faster and cheaper way to develop new medical treatments. In this paper, we present, to our knowledge, the first application of multiplex-heterogeneous network embedding to drug repositioning. Network embedding learns the vector representations of nodes, opening the whole machine learning toolbox for a wide variety of applications including link prediction, node labelling or clustering. So far, the application of network embedding for drug repositioning focused on heterogeneous networks. Our approach for drug repositioning is based on multiplex-heterogeneous network embedding. Such method allows the richness and complexity of multiplex and heterogeneous networks to be projected in the same vector space. In other words, multiplex-heterogeneous networks aggregate different multi-omics data in the same network representation. We validate the approach on a task of link prediction and on a case study for SARS-CoV2 drug repositioning. Experimental results show that our approach is highly robust and effective for finding new drug-target associations.

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89 % of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. Results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0 %, respectively. The method's robustness is demonstrated by the notable similarities between the calibrations carried out in two different equipment and institutions.

The world is suffering from the Coronavirus pandemic and is undergoing some drastic changes in day to day lives. The survey was conducted to analyze the situation of Pharmacy students in India. What are the types of challenges being faced by them during this lockdown due to the Pandemic COVID-19 and how are they getting adapted to the situations? A cross sectional survey was conducted via snowball sampling technique in which 226 participants submitted their response. The chief issue of concern to students was the change in the study pattern which has made the process much difficult for both the faculties and students. Online examination was also be reported as a point of concern. The normal life that we used to have is not acceptable in today’s scenario, hence, the institutions have to make the students more comfortable and adaptable towards the online studies and make the most out of it.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-67; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting. Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p<0.0001) or AZM+HCQ (p<0.0001). To improve the evidence level, a case-control analysis was performed on a sample of 57 patients (19/group) matched for age, sex and BMI. The statistical difference between NST and AZM was confirmed (p=0.0149) as well as the difference with AZM+HCQ (p=0.0002). No cardiac toxicity was recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model. In conclusion, AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.

Ligand and structure based virtual screening approaches were applied to clinical stage drugs as well as those approved for human use in an attempt to repurpose drugs for potential use against COVID-19. This approach involved ligand-based shape similarity searches, structure-based docking and pharmacophore searches with the help of pharmacophore queries derived from available ligands and receptor structures. Several compounds appeared as hits in pharmacophore and shape similarity searches and those docking to the SARS-CoV-2 viral 3CL protease were then ranked on the basis of docking scores.

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

The recent outbreak of coronavirus disease 2019 caused by the new coronavirus, SARS-CoV-2, has become an international emergency. Since there is no effective therapy for the treatment of this disease, drugs or vaccine that can prevent or cure the SARS-CoV-2 infection are urgently needed. The viral 3-chymotrypsin-like cysteine protease (3CLpro), which plays a key role in the replication of coronavirus, is a potential drug target for the development of anti-SARS-CoV-2 drugs. With the crystal structure of 3CLpro, we performed virtual screening from a small chemical library of a Traditional Chinese Medicine recipe- FuFang Zhenzhu Tiaozhi (FTZ). Five compounds with the best scores were screened and could be considered as potential hit compounds to be investigated further with bioassays for their anti-virus effects.

2019-nCoV, a novel coronavirus, caused the pneumonia outbreak in China and continue to expand. The host receptor for 2019-nCoV Angiotensin-converting enzyme 2 (ACE2), which is the same as the host receptor of SARS-CoV. Targeting ACE2 holds the promise for preventing 2019-nCoV infection. Chinese Medicine herbs could be a valuable pool for identifying active compounds for treating infection of 2019-nCoV. In this study, we summarize several active compounds including baicalin, Scutellarin, Hesperetin, Nicotianamine and glycyrrhizin that could have potential anti-2019-nCoV effects, and we conduct molecular docking to predict their capacity for binding ACE2, which may subsequently prevent the 2019-nCoV infection. We propose that these selected compounds worth further investigation for preventing 2019-nCoV.

In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.

Ever since pharmacy has become a profession, pharmacist's role has been continuously subjected to changes due to specific influences from historical, socio-economic, political, and scientific context. Nowadays the classic perception of pharmaceutical profession in Community Pharmacy is facing worldwide extinction due to many factors. Modern services, such as online, mail-order, and telephone-order pharmacies are increasingly gaining ground thanks to their ability to facilitate customer demand. However, at the same time, they are endangering “face-to-face” contact, affecting the building of customer loyalty based on direct “human” interaction, and consequently reducing pharmacists to mere commercial figures. Communication is in fact emphasized as the essential element to build a solid and appropriate interpersonal relationship with the client, to make the consultancy process effective, and to strengthen pharmacist's professionalism in community pharmacy. The aim of this work is to analyze pharmacist’s role in modern society by pinpointing the factors affecting pharmacy profession practice. Specific purpose will be improving both the academic training of future professionals and their capacity to approach public relations through a deepened study and practice of behavioral, communication, educational, and sociological methodologies and techniques that would allow the development of more effective communication skills useful for providing an efficient consultancy service.

Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement. Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.

This review aimed at defining and classifying extended spectrum β-lactamases, ESBLs and carbapenemases, summarizing the different phenotypic methods used to detect production of these enzymes in clinically significant gram negative bacteria and also describing the methods that discourse challenges mostly encountered during detection of these enzymes in microbiology laboratories with the purpose of formulating recommendations on best practice to screen for these enzymes. We conclude that the modified double disk synergy, MDDS is not only suitable for the confirmation of ESBL production after screening isolates with the cephalosporin/clavulanate combination disc diffusion or broth micro-dilution methods but also distinguishes ESBL production and over-expression of AmpC-derepressed mutants and as well serves as an indicator for AmpC screening. Furthermore, we suggest cefotaxime, ceftazidime and cefpodoxime (for testing using a single drug) as indicator antibiotics of choice for ESBL detection. The MDDS and cefoxitin/AmpC inhibitor combination disc method, using cloxacillin and phenylboronic acid can be used as screening tests for AmpC production and either the AmpC disc test, the disc approximation test or the modified three dimensional extract test as confirmatory tests for AmpC production. We also suggest that confirmation of carbapenemase production be done with the modified hodge test, using Klebsiella pneumoniae ATCC 700603 as the indicator organism or the modified carbapenem inactivation method. However, to differentiate between the different classes of carbapenemases, boronic acid and EDTA based methods (double-disk synergy tests and combined-disk tests) using imipenem, meropenem and ertapenem, in combination with 3-aminophenylboronic acid and ethylene diamine tetra acetic acid be used.

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

Background and objectives: Contrast-induced nephropathy (CIN), is an acute renal damage due to contrast agents. This study is conducted to determine the potential diagnostic value of hypoxia-inducible factor 2-alpha (HIF2-α) and to evaluate the renal protective effects of N-acetyl cysteine (NAC) and sildenafil in a rat CIN model. Material/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Totally, rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN+NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modelling, prophylactic treatment was performed at 24th and 48th hours. After 48 hours of the modelling; blood, urine, tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum and urine samples. Renal sections were performed in order for histopathologic and immunohistochemical evaluations. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC, efficiently decreased the renal damage due to contrast agents (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study constructs an experimental base for the use of HIF-2α for clinical prevention and treatment of CIN. Several mechanisms may be postulated for the changes in HIF-2α levels. Besides, the increased HIF-2α levels with CIN and decreased HIF-2α levels after treatment may be used for the treatment and follow-up of patients with CIN.

Background: Paracetamol may be use as antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain on post vaccination in infants. The use of Paracetamol during fever may be or may not be recommended since it may alter natural human body immune response although it may reduce pain. Objectives: This study described the relevancy of Paracetamol use post infants vaccination based on data collection systematic review analyses. This study aims to describe the effectiveness of breastfeeding in reducing pain and Paracetamol in reducing fever and pain post infants vaccination. Data Sources and Study Selection: Electronic literature search by hand searching six (6) databases which include Ovid LWW Total Access Collection and Medline, CINAHL (Cumulative Index to Nursing and Alled Health Literature) Plus with Fulltext, Science Direct, Proquest Dissertations and Theses, Proquest Education Journal and Proquest Health and Medical Complete. Additionally, manual reference checks of all articles on Paracetamol and breastfeeding post infants vaccination published in English Language between 1978 and 2017. Two level of screening were used on 9614 citations which include screening of abstracts and titles followed by full text screening. Data Synthesis: Data synthesis were tabulated into study characteristics, quality and effects. Authors of trials were not contacted for further details or provision of original data if the published report contained insufficient information. The study findings, as reported by the authors, were included in this review. The data in this research cannot be pool due to not enough data regarding odd ratio or relative risk as well as confidence interval in each study. Results: Systematic review of breastfeeding included three (3) studies from 9614 of database searching. The reviews of all these three (3) studies found significant benefit from breastfed in pain score and duration of crying as well as behavioral changes. None study stated the unbeneficial of breastfeeding before, during and after immunization. Meanwhile, systematic review of Paracetamol effectiveness included four (4) studies from 1177 of database searching. The reviews of two (2) studies found significant benefit from prophylaxis Paracetamol in fever and only one (1) study found significant benefit from prophylaxis Paracetamol in fussiness. On the other hand, there was one (1) study found not signifiant benefit from prophylaxis Paracetamol in fever. Other than that, there were two (2) studies evaluate the safety of prophylactic Paracetamol which revealed different outcomes, in which study by Prymula et. al. in 2009 found that antibody responses to several antigens were reduced significantly, and the other study by Uhari et. al. in 1988 found that antibody titres to DTP bacteria of placebo and PCM not differ significantly. Thus, Paracetamol seems to be not relevant post infants vaccination and breastfeeding was found to be beneficial post infants vaccination. Conclusions: The relevancy of giving Paracetamol post all types of vaccination may be questionable since the safety issue of this intervention may be arised. Breastfeeding before, during and after immunization are recommended for pain reduction as it was proved effectively. Finally, in deciding Paracetamol to be of rational use following infants immunization, it may need for further research which include in depth quantitative and qualitative studies to identify specific problem and causes regarding this issue.

Borneol and menthol were two terpenes wildly used as penetrate enhancer in transdermal drug delivery. To explore their penetration enhancement effect towards hydrophilic drug, 5-FU was selected as model drug. A method combined vitro permeation studies and coarse grain molecular dynamics was used to investigate their penetration enhancement effect towards 5-FU. As a result, although both borneol and menthol showed a penetration enhancement effect towards 5-FU, they differed a lot in the penetration enhancement mechanism, which was also thought to account for their different penetration enhancement effect. As for menthol, SC bilayer disrupting effect seemed to be its main mechanism. While for borneol, its mechanism seemed to be more complicated. Except for disrupting the SC bilayer, it could also increase the permeation of 5-FU by enhancing the diffusion rate of 5-FU or inducing the formation of transient pore. All of this enable us a molecular understanding of borneol and menthol’s penetration enhancement effect towards hydrophilic drug, which might provide some guidance in the latter research and application.

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.