Massoia (Massoia aromatica Becc., Lauraceae) bark has been widely used as a component of traditional Indonesian medicine. The indigenous people boil or steam the bark for traditional applications. Our preliminary research revealed the potency of Massoia essential oil and its major compound, C-10 Massoialactone as potential immunomodulator in vitro. However, no scientific evidence regarding its in vivo effects is available. Therefore, this study evaluated the potential immunomodulatory effects of Massoia bark infusion on the nonspecific immune response (phagocytosis) of Wistar rats. The aqueous extract of Massoia bark was obtained by boiling pulverized bark in water, and the C-10 massoialactone content of the extract was determined through Thin Layer Chromatography (TLC) densitometry. For the in vitro assay, macrophages were treated with the freeze-dried infusion at the concentrations of 2.5, 5, 10, 20, or 40 μg/mL media. For the in vivo assay, 2-month-old male Wistar rats were divided into 5 groups. The baseline group received distilled water at the dose of 1 mL/100 g BW with the immunostimulant herbal product “X” administered as the positive control at the dose of 0.54 mL/rat. The treatment groups received the infusion at a dose of 100, 300, or 500 mg/100 g BW. Treatments were given orally every day for 14 days. The ability of macrophage cells to phagocyte latex was determined as phagocytic index (PI) and was observed under microscopy with 300 macrophages. The in vitro study revealed that the phagocytic activity of the infusion-treated macrophages significantly increased in comparison with that of the control macrophages in a concentration-dependent manner. Among all treatment concentrations, the concentration of 40 μg/ml provided the highest activity with a PI value of 70.51% ± 1.11%. The results of the in vivo assay confirmed those of the in vitro assay. The results of the present study indicate that Massoia bark can increase the phagocytic activity of rat macrophage cells. Its potential as a naturally derived immunomodulatory agent requires further study.

Natural products are considered an essential source of chemical compounds with relevant biological activities. Important antibiotics, anti-virals, and anticancer agents within healthcare facilities have been isolated from them. In recent decades, the study of alkaloids and the modulation of the immune response has aroused interest. The survey of SAR alkaloids with immunomodulatory effects is of great importance since structural modifications impact the effectiveness of the immunomodulatory activity, thus promoting the rational design of more effective and specific drugs. This review exhibits the main alkaloids with an immunomodulatory effect and their relationship with SAR studies, particularly in activating leukocytes and secretion of molecules with critical inflammatory activities such as cytokines, chemokines, and nitric oxide. These studies optimize the properties of alkaloids and allow a deeper understanding of the mechanisms of action at a molecular level, which is fundamental for the innovation of immunological therapies.

Polysaccharide from Ficus carica L. (FCP) exert multiple biological activities, as a biological macromolecule, the available knowledge about the specific structures and mechanisms of biological activity of purified 'Brunswick' fig polysaccharide is currently limited. In the present study, by chemical purification and characteristics identified via specific instruments, and then the impact of FCP on the immunomodulation activity in vitro and in vivo was examined. Structural char-acteristics showed that the molecular weight of the FCP was determined to be 127.5 kDa, the primary monosaccharides present in the FCP were galacturonic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), and xylose (Xyl) at a ratio of 0.321:0.287:0.269:0.091:0.013:0.011. Based on the investigation of in vitro immunomodulatory ac-tivity, FCP was found to stimulate the production of NO, TNF-α, and IL-6 and increased the pi-nocytic activity of macrophages. Further analysis revealed that FCP activated macrophages by interacting with toll-like receptor 4 (TLR4). Moreover, the in vivo test results indicate that FCP showed significant increase serum pro-inflammatory factors in immunosuppressed mice. Overall, this study suggests that FCP has the potential to be utilized as a novel immunomodulator in the pharmaceutical and functional food industries.

(1) Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neu-roinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. (2) Methods: EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV's impact on TREM2 and behavior. TREM2 and related gene expressions were examined in mono-cyte-derived macrophages (MDMs) from PWH (n=42) and people without HIV (PWoH; n=19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. (3) Results: EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially re-versed by CBD. (4) Conclusions: These findings suggest HIV affects TREM2 expression modu-lated by cannabis and CBD, offering insights for therapeutic strategies.

Lasiodiplodan, an exocellular Lasiodiplodia theobromae β-glucan exopolysaccharide (LaEPS), has at-tracted interest because of its antioxidant, antimicrobial, anti-inflammatory, and antiproliferative properties. LaEPS carboxymethylation enhances LaEPS water solubility and biological activities. However, carboxymethylated fractions of LaEPS (LaEPS-C): LLaEPS-C (Linear) and BLaEPS-C (Branched) were not widely studied yet. So, LaEPS-C, LLaEPS-C, and BLaEPS-C were assessed for their antioxidant, antimicrobial, antiproliferative, anticoagulant, immunomodulatory, and anti-viral activities. Elementary Chemical Composition Analysis confirmed their structural charac-teristics by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), Nuclear Magnetic Resonance (NMR), and Scanning Electron Microscopy (SEM) techniques. The best DPPH scavenging potential was achieved for LLaEPS-C for concentrations lower than 200mg/mL. LaEPS-C showed moderate antiproliferative activity for the NCI-ADR/RES cell (GI50 65.3 µg/mL), and BLaEPS-C showed weak activity for the K562 cell (GI50 235 µg/mL). LLaEPS-C had a reduced Prothrombin Time (PT) and a procoagulant effect. LLaEPS-C and BLaEPS-C are inducers of pro-inflammatory activity due to their ability to induce TNF-α in human macrophages. LLaEPS-C also showed anti-hRSV, which confirmed the antiviral activity of this molecule.

Corona Virus disease 2019 (COVID-19) is a new strain of coronavirus that causes respiratory illnesses with a start of flu like symptoms. This disease is fatal and is spread all over the world. The Scientist are working day and night to find vaccine or a cure. World Health Organisation has declared COVID-19 as pandemic [1]. In the view of the pandemic many treatments are being tried on the patients and various treatment modalities are being followed, the traditional medicine has shown a major role to manage this disease. The traditional medicines include the use of herbs, nutrition and spices that are freely available in Asian countries. These are used in day to day life by Asian population [2]. In this paper we have compiled and reviewed the role of various herbs and spices such as Oregano, Ashwagandha, Ginseng, Basil, Sage, Curcumin, Fenugreek, Ginger and Garlic in building immunity and also in curing pathogenic invasions based on evidence based researches. As there is no cure available for COVID-19 till now so supportive therapy is playing a major role for the patients to fight with this pandemic. The AYUSH ministry has also promoted the use of above herbs for a patient suffering from this disease. The corona virus is present in respiratory system as shown by different studies and it has different strains. The guidelines laid by the ICMR and WHO shows that use of herbs, spices and nutrients can be helpful to manage this virus by increasing the immunity in patients. Hence we are not claiming any cures but the herbs and spices used in day to day life are very much effective in management of COVID-19. World Health Organisation (WHO) has recognised the use of alternative and traditional medicine in the management of COVID-19 but the herbs should be used in prescribed amounts and overdose of them can be harmful for health [1,3]. Therefore the present article will enlighten the readers about the role of herbs, spices and nutrients in improving the conditions in COVID-19.

Objectives: This study aimed to evaluate the potential of poplar-type propolis for wound healing by analyzing its phytochemical profile and biological effects. Methods: The phytochemical characterization included specific colorimetric assays to estimate the total phenolic and flavonoid contents and the triterpenoids content. Some of the main components of poplar propolis (pinocembrin, pinobanksin, CAPE, chrysin, galangin) were analyzed using HPLC-DAD. Scavenging activity and total antioxidant capacity were assessed through DPPH and ORAC assays, respectively. Biological in vitro assays used keratinocyte, fibroblast, and monocytic cell lines. The direct wound healing properties were tested through scratching assays and ELISA kits for the assessment of the production of growth factors (FGF-7, Latency Associated Peptide - LAP), while the indirect effects were evaluated through the estimation of the levels of MMP9, IL-1β, IL-8 and TNF-α using ELISA kits together with a cell-free test on the inhibition capacity on collagenases. During the study, the Network Pharmacology analysis was employed to further explore possible mechanisms of action of propolis on the healing process. Results: The analyses confirmed the high phenolic content of poplar propolis, dominated by flavonoids, and terpenes. Propolis exhibited significant antioxidant activity and interestingly, propolis showed indirect wound-healing properties by mitigating inflammation and remodeling (reduced IL-1β and MMP9) and potentially modulating the immune response (upregulated IL-8). In vitro studies confirmed these effects, demonstrating decreased MMP9 production and collagenase inhibition when cells were co-treated with propolis and a stressor. Propolis also suppressed IL-1β release in fibroblasts, although its impact on TNF-α was inconclusive. Notably, co-treatment upregulated IL-8 in monocytes, suggesting a potential immunomodulatory role. Conclusion: poplar propolis may not directly stimulate cell proliferation during wound healing, while its anti-inflammatory and immunomodulatory properties could suggest an indirect contribution to the process.

Monomeric Ubiquitin (Ub) is a 76-amino acid highly conserved protein found in eukaryotes. The first described biological activity of Ub in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, cardio- and brain-protective agent.

Selenium (Se) is an essential trace element for human beings and Se supplementation is of great significance. In this paper, high selenized Gastrodia elata Blume Polysaccharides (SeGEP) were obtained through pre-sulfation before conducting the selenylation modification process, which owned a maximum Se content reach to 2.29%. UV, FT-IR, NMR, SEM, EDX, HPLC, size-exclusion chromatography and periodate oxidation analysis showed that the seleninic group had been successfully introduced into GEP with the substitution position at C-6 of glucose. Immunostimulating assays were conducted in vitro and in vivo on RAW 264.7 cells and cyclophosphamide (CTX)-induced mice model, respectively. The results showed that Se-GEP enhanced RAW264.7 cells proliferation, cell phagocytosis, and secretion of nitric oxide (NO) and interleukin (IL)-1β factors. In addition, Se-GEP enhanced the immunologic activity of CTX-treated mice by increasing the spleen and thymus indices, enhancing the phagocytic function, and activating both Th1 and Th2 lymphocytes. The current outcome also suggested that Se-GEP with covalently bonding Se group possessing increased safety and has a potential dietary selenium nutrient for improving human immunity.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group: received PBS orally; prevention group: oral administration of MOG35-55 two weeks before EAE induction; treatment group: oral administration of MOG35-55 after EAE induction. MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-β, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Background: While several drugs are in the pipeline for treatment of various grades of COVID-19 disease, none of them have shown promise until now. Medicinal plants are crucial in developing and developed countries for their primary and basic health needs owing to better tolerability, superior compatibility with human body and having lesser side effects. AEV01 , a speciality extract of kutki (Picrorhiza kurroa), is one potential medicinal herb which can be effective for mild COVID19 in elderly patients at risk of complications and aging immunity. Purpose: The efficacy and safety of AEV01 for mild COVID-19 in elderly patients at risk of complications was investigated in this study. Study design: A prospective, phase 3, randomized, multicentric, placebo controlled double blinded parallel group interventional trial. Methods: This study was conducted in elderly patients diagnosed as COVID-19 with mild symptoms. 70 patients were randomized into two groups to receive AEV01 capsule (100mg) and placebo respectively thrice daily for 30 days along with standard care of treatment as per national WHO/ICMR guidelines. Clinical improvement timelines and corresponding scores using 8-point ordinal scale and NEWS were assessed for efficacy and safety of AEV01 in COVID-19 patients. Results: AEV01 group showed a significant improvement (P=0.0001) in the normalization of the SpO₂ rate and relief from cough. There was also significant difference in time to recovery, with patients in the AEV01 drugtreated group recovering in 4.5 days as compared to Placebo in 9.1 days. ESR, LDH, serum ferritin, Neutrophil-Lymphocyte ratio (NLR), TNF- alpha, IL-6 and CD4 cell counts, which are considered as prognostic markers in COVID19 infected patients, showed a significant improvement in patients treated with AEV01. The AEV01 drug treated group showed significant clinical improvement in the 8-point ordinal scale severity rating and NEW Score from day 3 onwards which continued up to end of study. Conclusion: AEV01 has shown a significant improvement in clinical and laboratory parameters. There was also reduction in the progression of the COVID-19 disease in unvaccinated elderly patients from mild to moderate when treated at an earlier stage.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

This paper continues the review study on antimicrobial properties relevant to the periodontal diseases. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response has been covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies has been analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there is still much less studies using animal models and only a few clinical studies. Most of the studies, regardless of the used model indicated efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontitis is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.

Amyotrophic lateral sclerosis (ALS) is also called "motor neuron disease”. In this review, we propose that ALS is not just a neuromotor disorder, but begins as a disorder of P53-modulated skeletal muscle metabolism, leading to failures at the energy state of the cells, incorrect redox states, motor denervation, and a loss of muscle fibers. Motoneurons die as a consequence of the lack of muscular feedback, and the oligomeric TDP43 aggregates progressively and relentlessly lead to mistakes in peripheral immune self-tolerance sustained over time. An effective treatment has not been found for this devastating pathology, as for 152 years the target has not been accurately defined. Scientists and doctors should consider new knowledge regarding ALS and consider immunomodulatory therapies that, based on genetic analysis and symptoms, can be combined with compounds that regulate metabolism and promote the elimination of useless organelles and cells. What if ALS could be cured as a result of seeing motor neuron disease differently? This review aims to develop that goal and change the paradigm of our understanding of ALS.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

Breast implant surgery has evolved significantly, yet challenges such as capsular contracture remain a persistent concern. This review presents an in-depth analysis of recent advancements in understanding the immune mechanisms and clinical implications associated with breast implants. The article systematically examines the complex interplay between immune responses and capsular fibrosis, emphasizing the pathophysiological mechanisms of inflammation in the etiology of this fibrotic response. It discusses innovations in biomaterial science, including the development of novel anti-biofilm coatings and immunomodulatory surfaces designed to enhance implant integration and minimize complications. Emphasis is placed on personalized risk assessment strategies, leveraging molecular insights to tailor interventions and improve patient outcomes. Emerging therapeutic targets, advancements in surgical techniques, and the refinement of post-operative care are also explored. Despite notable progress, challenges such as variability in immune responses, long-term efficacy of new interventions, and ethical considerations remain. Future research directions are identified, focusing on personalized medicine, advanced biomaterials, and bridging preclinical findings with clinical applications. As we advance from bench to bedside, this review illuminates the path forward, where interdisciplinary collaboration and continued inquiry weave together to enhance the art and science of breast implant surgery, transforming patient care into a realm of precision and excellence.