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Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIVs impact on TREM2 and behavior. TREM2 and related gene expressions were examined in monocyte-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. 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 in PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

Objective: Cyclophosphamide (CTX) is an effective anticancer drug, but toxic effects against normal human tissues are its dose-limiting drawback. The aim of this research was to investigate the in vivo immunomodulatory activities of Allium ampeloprasum Subsp Iranicum against CTX-induced toxicity in mice. Materials and Methods: Extract of the whole plant of A. ampeloprasum Subsp Iranicum was obtained using the maceration technique, and its total phenolic and flavonoid contents were quantified through spectrophotometric analysis. Mice received daily oral administration (PO) of the extract (150 mg/kg) for a duration of 14 days, either as a standalone treatment or in conjunction with an intraperitoneal (IP) injection of 20 mg/kg CTX. The effects of the extract on body weight, spleen weight, white blood cell (WBC), serum antibody titer hemagglutination (HA), delayed-type hypersensitivity response (DTH), lymphocyte proliferation, cytokine production, and histopathological examinations were evaluated. Results: A. ampeloprasum Subsp Iranicum restored several parameters including spleen weight (p<0.001), WBC (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01), HA titer (p<0.05), and DTH response (p<0.01). A. ampeloprasum Subsp Iranicum notably stimulated lymphocyte proliferation to PHA (p<0.01) and LPS (p<0.05) and recovered interferon (IFN)-γ (p<0.001) and interleukin (IL)-4 (p<0.001) levels in the immunosuppressed mice. Also, CTX-induced histopathological changes were reversed by A. ampeloprasum Subsp Iranicum . Conclusion: Analyses revealed A. ampeloprasum Subsp Iranicum could regulate immunity and increase host immune responses. The observed strengthening effect can be attributed to the high amount of flavonoids and dipropyl trisulfide compounds present in A. ampeloprasum Subsp Iranicum. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the immunomodulatory function and safety of compound preparation containing Ganoderma lucidum polysaccharides. Methods: According to the Technical Standards for Testing and Assessment of Health Food (2003 Edition), the immunomodulatory function of compound preparation containing Ganoderma lucidum polysaccharides was evaluated comprehensively from cellular immunity, humoral immunity and non-specific immunity by measuring the ability of lymphocyte proliferation, degree of ear swelling, number of hemolytic plaques, phagocytic percentage, phagocytic index and natural killer (NK) cells activity in normal mice. Its safety was evaluated comprehensively by acute oral toxicity test in mice, Ames test and 30 d feeding test in rats. Results: In cellular immunity test, the tested substance had no significant effect on lymphocyte proliferation induced by concanavalin A and degree of ear swelling (P>0.05). In the humoral immunity test, the low dose group (0.17 g/kg), the middle dose group (0.33 g/kg) and the high dose group (1.00 g/kg) could increase the level of antibody-producing cells by 10.98%, 12.08%, 17.63% (P<0.05). In the non-specific immunity test, the middle dose group and the high dose group could significantly increase the phagocytosis ability of mononuclear macrophages (P<0.05) and the activity of NK cells (P<0.01). The maximum tolerance dose (MTD) of the tested substance to the acute oral dose of both male and female mice was more than 42.56 g/kg, which belonged to non-toxic substances. The results of Ames test were negative and no mutagenicity was found. In the 30 d feeding test, each dose group had no significant effect on body weight, weekly food utilization rate, blood routine index, blood biochemical index and main organ coefficient (P>0.05), and no obvious pathological changes were found by histological examination. Conclusion: Compound preparation containing Ganoderma lucidum polysaccharides had a positive effect on immunomodulatory function in mice, and it had a good safety as a health food. [ABSTRACT FROM AUTHOR]

Background: Lactiplantibacillus species are extensively studied for their ability to regulate host immune responses and functional therapeutic potentials. Nevertheless, there is a lack of understanding on the mechanisms of interactions with the hosts during immunoregulatory activities. Methods: Two Lactiplantibacillus plantarum strains MKMB01 and MKMB02 were tested for probiotic potential following Indian Council of Medical Research (ICMR) guidelines. Human colorectal adenocarcinoma cells such as HT-29, caco-2, and human monocytic cell THP-1 were also used to study the potential of MKMB01 and MKMB02 in regulating the host immune response when challenged with enteric pathogen Salmonella enterica typhimurium. Cells were pre-treated with MKMB01 and MKMB02 for 4 h and then stimulated with Salmonella. qRT-PCR and ELISA were used to analyze the genes and protein expression. Confocal microscopy and field emission scanning electron microscopy (FESEM) were used to visualize the effects. An Agilent Seahorse XF analyzer was used to determine real-time mitochondrial functioning. Results: Both probiotic strains could defend against Salmonella by maintaining gut integrity via expressing tight junction proteins (TJPs), MUC-2, and toll-like receptors (TLRs) negative regulators such as single Ig IL-1-related receptor (SIGIRR), toll-interacting protein (Tollip), interleukin-1 receptor-associated kinase (IRAK)-M, A20, and anti-inflammatory transforming growth factor-β and interleukin-10. Both strains also downregulated the expression of pro-inflammatory cytokines/chemokines interleukin-1β, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor-alpha (TNF-α), interleukin 6, and nitric oxide (NO). Moreover, TNF-α sheddase protein, a disintegrin and metalloproteinase domain 17 (ADAM17), and its regulator iRhom2 were downregulated by both strains. Moreover, the bacteria also ameliorated Salmonella-induced mitochondrial dysfunction by restoring bioenergetic profiles, such as non-mitochondrial respiration, spare respiratory capacity (SRC), basal respiration, adenosine triphosphate (ATP) production, and maximal respiration. Conclusions: MKMB01 and MKMB02 can reduce pathogen-induced gut-associated disorders and therefore should be further explored for their probiotic potential. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Regulation of the immune system to maintain homeostasis in the organism has become a focus of research, and the synergistic effect of multi‐component complexes will effectively improve the immunomodulatory activity. The present study aimed to investigate the interaction and synergistic immunomodulatory activity of isochlorogenic acid A (IAA) and Lycium barbarum glycopeptide (LbGp).The results obtained indicated that non‐covalent intermolecular interactions were employed to form the LbGp–IAA complex, with a binding ratio of 135.15 mg g−1. The formation of LbGp–IAA complex altered the conformation of LbGp, and IAA was mainly bound to LbGp by van der Waals forces and hydrogen bonds. In addition, LbGp–IAA promoted the proliferation of RAW264.7 cells. The IAA and LbGp interaction had a synergistic effect on the promotion of phagocytosis and the expression of nitric oxide, tumor necrosis faction‐α and interleukin‐1β, which improved the immunomodulatory effect of LbGp. Furthermore, the combination of LbGp and IAA synergistically inhibited lipopolysaccharide‐induced inflammatory response.In summary, the binding of IAA enhanced the immunomodulatory activity of LbGp and coordinated the immune response, and did not trigger an inflammatory response, which was potentially attributed to the alteration of spatial structure of LbGp through the binding of IAA. The results provide new perspectives for the study of glycopeptide–polyphenol interactions. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSMilk fat globule-epidermal growth factor 8 (MFG-E8) is a multifunctional glycoprotein regulating intercellular interactions in various biological and pathological processes. This review summarizes the effects and mechanisms of MFG-E8 in neurodegenerative diseases (NDDs), emphasizing its roles in inflammation, apoptosis, and oxidative stress. In this review, will also explore the potential of MFG-E8 as a diagnostic biomarker and its therapeutic applications in neurodegenerative disorders. Recent studies have revealed intriguing characteristics of using MFG-E8 as a potential drug for treating various brain disorders. While the discovery, origin, expression, and physiological functions of MFG-E8 in various organs and tissues are well defined, its role in the brain remains less understood. This is particularly true for NDDs, indicating unmet medical needs. Elucidating its role in the brain could position MFG-E8 as a potential treatment for NDDs.The expression and regulation of MFG-E8 in neurodegenerative diseases.The role of MFG-E8 in the mechanisms of neurodegenerative diseases.Potential application challenges and strategies for MFG-E8 as a therapeutic target.The expression and regulation of MFG-E8 in neurodegenerative diseases.The role of MFG-E8 in the mechanisms of neurodegenerative diseases.Potential application challenges and strategies for MFG-E8 as a therapeutic target. [ABSTRACT FROM AUTHOR]

Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration of cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, and lysosomal phagocytosis, oligonucleotide therapy remains a formidable challenge. The discovery of cationic peptides has provided innovative insights for the effective delivery of oligonucleotides, yet the stable, efficient, and convenient assembly of peptides and oligonucleotides remains an elusive goal, referred to as the "Holy Grail" challenge in the field. Addressing this challenge, it has pioneered the development of a straightforward and highly efficient engineering carrier‐free covalent peptide‐oligonucleotide nano‐conjugates (PONs) through a mild click reaction. Notably, this PONs can realize self‐assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase resistance and surprisingly effective intracellular oligonucleotide delivery as well as lysosomal escape. Based on this strategy, a PONs named CPP‐(DOPA)6‐miRNA‐223 is synthesized, which demonstrates rapid and effective cellular uptake, swift lysosomal escape in macrophage, remarkable accumulation in inflammatory regions and excellent therapeutic effect in an inflammatory arthritis model. Therefore, this work may provide a breakthrough for the clinical application of all oligonucleotide delivery therapies and expanding the applications in gene therapy. [ABSTRACT FROM AUTHOR]

Vernonia cinerea L., also known as purple fleabane, is a plant with medicinal properties that have been traditionally used to treat respiratory infections, digestive disorders, and skin conditions. Its antimicrobial and antiinflammatory properties make it a potential candidate for treating various infections and inflammatory diseases. The plant contains alkaloids, flavonoids, and essential oils, which possess antimicrobial properties, making it a promising candidate for treating bacterial and fungal infections. Its anti-inflammatory properties have shown potential for managing inflammatory diseases like arthritis and dermatitis. Additionally, the plant's analgesic and antipyretic effects suggest its potential for pain management and fever reduction. Its antioxidant properties make it a potential candidate for preventing and treating oxidative stress-related diseases like cardiovascular disorders and neurodegenerative conditions. However, more studies are needed to determine its optimal dosage, safety profile, and potential drug interactions before widespread use in medical practice. [ABSTRACT FROM AUTHOR]

The colonization ability of Limosilactobacillus fermentum DALI02 and the promoting effect of fermented prebiotics have been studied. This study aims to evaluate the systemic immunomodulatory effects of DALI02 and DALI02 + Prebiotics on cyclophosphamide‐induced immunosuppressed rats. We found that DALI02 and DALI02 + Prebiotics, especially DALI02 + Prebiotics, exhibited significant restorative effects on the immunocompromised state in rats (p <.05). Specifically, both of them promoted the recovery of body weight and immune organ function, enhanced the proliferative capacity of immune cells, and effectively reduced the levels of interleukin 6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). Furthermore, both of them significantly reduced the levels of lipopolysaccharide (LPS) and D‐lactic acid in the blood (p <.05). Principal coordinate analysis (PCoA), principal component analysis (PCA), and unsupervised cluster analysis revealed that DALI02 and DALI02 + Prebiotics group were more similar to the blank group at the genus level of the gut microbiota. At the level of short‐chain fatty acids (SCFAs), DALI02 + Prebiotics and blank group belonged to Cluster 3. These results suggested that the intervention with DALI02 and DALI02 + Prebiotics effectively modulated the structure of the gut microbiota, and DALI02 + Prebiotics restored the dysregulation of SCFAs. In summary, DALI02 and DALI02 + Prebiotics possess immunomodulatory functions, with the latter showing superior effects. [ABSTRACT FROM AUTHOR]

Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor‐mediated activation and environmental cues. This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C‐type lectin‐like receptor 2 and combining all thrombin‐collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor‐induced PEVs. Our findings underscore that PEVs are tunable through receptor‐mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative. [ABSTRACT FROM AUTHOR]

In this study, a mixture of Platycodon grandiflorum, Pyrus serotina, Chaenomeles sinensis, and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E2 (PGE2) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4. PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages. [ABSTRACT FROM AUTHOR]

Background and purpose: In October 2020, the European Academy of Neurology (EAN) consensus statement for management of patients with neurological diseases during the coronavirus disease 2019 (COVID‐19) pandemic was published. Due to important changes and developments that have happened since then, the need has arisen to critically reassess the original recommendations and address new challenges. Methods: In step 1, the original items were critically reviewed by the EAN COVID‐19 Task Force. In addition, new recommendations were defined. In step 2, an online survey with the recommendations forged in step 1 was sent to the Managing Groups of all Scientific and Coordinating Panels of EAN. In step 3, the final set of recommendations was made. Results: In step 1, out of the original 36 recommendations, 18 were judged still relevant. They were edited to reflect the advances in knowledge and practice. In addition, 21 new recommendations were formulated to address the new knowledge and challenges. In step 2, out of the 39 recommendations sent for the survey, nine were approved as they were, whilst suggestions for improvement were given for the rest. In step 3, the recommendations were further edited, and some new items were formed to accommodate the participants' suggestions, resulting in a final set of 41 recommendations. Conclusion: This revision of the 2020 EAN Statement provides updated comprehensive and structured guidance on good clinical practice in people with neurological disease faced with SARS‐CoV‐2 infection. It now covers the issues from the more recent domains of COVID‐19‐related care, vaccine complications and post‐COVID‐19 conditions. [ABSTRACT FROM AUTHOR]

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising tool in the field of regenerative medicine due to their unique therapeutic properties as they can differentiate into multiple cell types and exert paracrine effects. However, despite encouraging results obtained in preclinical studies, clinical trials have not achieved the same levels of efficacy. To improve the therapeutic properties of MSCs, several strategies have been explored. Therefore, in this review, the therapeutic properties of MSCs will be analyzed, and an update and overview of the most prominent approaches used to enhance their therapeutic capabilities will be provided. These approaches include using drugs, molecules, strategies based on biomaterials, and modification parameters in culture. The strategy described shows several common factors among those affected by these strategies that lead to an enhancement of the MSCs therapeutic properties such as the activation of the PI3K/AKT pathway and the increased expression of Heat Shock Proteins and Hypoxia-Inducible Factor. The combined effect of these elements shift MSCs towards a glycolytic state, suggesting this shift is essential for their enhancement. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis aimed to summarize the immunomodulatory effect of Huaier (Trametes robiniophila Murr) granule as adjuvant therapy in patients with cancer. Materials and methods: Two authors conducted a search for literature indexed on various databases including PubMed, Embase, Cochrane Library, CNKI, Sinomed, VIP, and WanFang. Randomized controlled trials (RCTs) that investigated the immunomodulatory effect of Huaier granule as adjuvant therapy in cancer patients were included. The outcome of interest included T-lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+/CD8+), immunoglobulin (IgA, IgG, IgM), and natural killer (NK) cells. Results: We identified 29 RCTs involving a total of 2206 cancer (including hepatocellular, breast, gastric, colorectal, lung, or nasopharyngeal carcinoma) patients. Compared with conventional treatment alone, Huaier combined conventional treatment significantly improved CD3+ (mean difference [MD] 6.95; 95% confidence intervals [CI] 4.42–9.48), CD4+ (MD 5.53; 95%CI 4.22–6.83), CD4+/CD8+ (MD 0.35; 95%CI 0.25–0.45), IgA (standardized mean difference [SMD] 1.18; 95%CI 0.44–1.93), IgG(SMD 1.71; 95%CI 1.11–2.30), IgM (SMD 0.83; 95%CI 0.59–1.07), and NK cells (MD 5.01; 95%CI 3.61–6.40). However, the effect of Huaier on CD8+ (MD − 1.35; 95%CI − 2.80 to 0.11) was not statistically significant between the groups. Conclusions: Huaier granule as adjuvant therapy may significantly improve immune function in patients with cancers. However, additional well-designed RCTs are needed to validate the current findings considering the methodological flaws of the analyzed trials. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have shown a positive effect on Osteoarthritis (OA), but the efficacy is still not significant in clinical. Conventional two-dimensional (2D) monolayer culture method is prone to cause MSCs undergoing replication senescence, which may affect the functions of MSCs. Three-dimensional (3D) culture strategy can sustain cell proliferative capacity and multi-differentiation potential. This study aimed to investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured by 3D hanging drop method on OA. Methods: hUC-MSCs were isolated from umbilical cord and cultured by 3D hanging drop method for 48 h. Scanning electron microscopy (SEM) was used to observe gross morphology 2D and 3D hUC-MSCs. Transcriptome comparison of gene expression differences between 2D and 3D hUC-MSCs. GO enrichment analysis, KEGG pathway enrichment analysis and GSEA enrichment analysis were used to analyze the impact of 3D hanging drop culture on the biological functions of hUC-MSCs. Female New Zealand rabbits (n = 12) were divided into 4 groups: Normal group, Model group, 2D hUC-MSCs treatment group and 3D hUC-MSCs treatment group. After 8 weeks, the gross and histological appearance of the cartilage was evaluated by safranin O-fast green staining and Mankin scoring system. The expression of type I collagen and type II collagen was detected by immunohistochemistry. The levels of IL-6, IL-7, TNFα, TGFβ1 and IL-10 in the knee joint fluid were tested by ELISA. Results: 3D hanging drop culture changed cell morphology but did not affect phenotype. The MSCs transcriptome profiles showed that 3D hanging drop culture method enhanced cell-cell contact, improved cell responsiveness to external stimuli and immunomodulatory function. The animal experiment results showed that hUC-MSCs could promote cartilage regeneration compared with Model group. 3D hUC-MSCs treatment group had a higher histological score and significantly increased type II collagen secretion. In addition, 3D hUC-MSCs treatment group increased the expression of anti-inflammatory factors TGFβ1 and IL-10. Conclusion: The above experimental results illustrated that 3D hanging drop culture method could enhance the therapeutic effect of hUC-MSCs, and showed a good clinical application prospect in the treatment of OA. [ABSTRACT FROM AUTHOR]

Diarrheal diseases remain the leading cause of high mortality among the infants, particularly in the developing countries; Probiotic intervention for diarrhea has been an ongoing novel approach to diarrheal prevention and treatment. This study aims to characterize immunogenic and probiotic properties of lactic acid bacteria (LAB) isolated from human breast milk and neonates' faeces. The LAB isolates from 16 mothers' breast milk and 13 infants' faeces were screened and identified by 16 S rRNA gene partial sequencing. Their antimicrobial activities against 5 strains of diarrheagenic Escherichia coli were tested. Organic acids production was quantified by HPLC, and antibiotic resistance pattern were determined by VITEK®. Autoaggregation, co-aggregation and hydrophobicity properties were assessed by UV spectrophotometry and immunomodulatory effect was determined in mouse model. Ninety-three LAB of five genera were identified. The most abundant species was Lactiplantibacillus plantarum with inhibition zones ranged from 8.0 to 25.0 ± 1 mm. Lacticaseibacillus rhamnosus A012 had 76.8 mg/mL lactic acid, (the highest concentration), was susceptible to all antibiotics tested. L. plantarum A011 and L. rhamnosus A012 were highly resistance to gastrointestinal conditions. L. rhamnosus A012 produced hydrophobicity of 25.01% (n-hexadecane), 15.4% (xylene) and its autoaggregation was 32.52%. L. rhamnosus A012 and L. plantarum A011 exert immunomodulatory effects on the cyclophosphamide-treated mice by upregulating anti-inflammatory cytokine and downregulating proinflammatory cytokines. Lactobacillus sp. demonstrated good probiotic and immunomodulatory properties. Further works are ongoing on the practical use of the strains. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. Infection with virulent strains of T. gondii induces excessive production of pro-inflammatory cytokines and increases fatality. Propolis has potential as an anti-inflammatory and immunomodulator. Aim: This study aimed to evaluate the pro-inflammatory cytokines response of Interleukin-2 (IL-2) and IL-17, and the anti-inflammatory cytokine IL-10 in mice infected with T. gondii RH strain and treated with ethanol extract of Trigona bee propolis (EEP) from Lombok, West Nusa Tenggara (NTB), Indonesia. Methods: A total of 36 mice were divided into six groups with six mice per group. Group 1 was considered as a negative control; mice were not infected and not treated while in groups 2 to 6, mice were infected with 100 T. gondii (tachyzoites). Mice in group 2 were infected but not treated whereas in groups 3, 4, 5, and 6, respectively, were treated orally with Cotrimoxazole 40 mg/kg body weight, EEP 1 mg, EEP 2 mg, and EEP 4 mg, the day after infection for 3 days. All mice under study were euthanized following ethical considerations with prior approvals, on the fifth day post-infection and spleens were taken to observe cytokines using flow cytometry. Statistical analysis was performed with one-way ANOVA and Duncan Multiple Range Test (you may add any statistical tool/software if used Like R version?, SPSS, version? If you used any of these/others)? Results: EEP (1-4 mg) increased CD4+ T cells, CD8+ T cells, and CD11b+ cells in infected mice, though not significantly (p > 0.05), unlike cotrimoxazole, which showed significant increases (p < 0.05). EEP at 2 mg and 4 mg (G5 and G6) reduced IL-2 and IL-17 in CD4+ T cells, and at 4 mg (G6) in CD8+ T cells. IL-10 expression increased in CD11b+ cells at 1 mg and in CD4+ T cells at 4 mg (G6). Conclusion: Propolis ethanol extract from Trigona spp. bees acts as an immunomodulator and anti-inflammatory in T. gondii-infected mice, supporting its potential as an anti-toxoplasmosis agent. [ABSTRACT FROM AUTHOR]

Stem cell therapy and skin substitutes address the stalled healing of chronic wounds in order to promote wound closure; however, the high cost and regulatory hurdles of these treatments limit patient access. A low‐cost method to induce bioactive healing has the potential to substantially improve patient care and prevent wound‐induced limb loss. A previous study reported that bioactive factors derived from apoptotic‐like mesenchymal stem cells (MSCs) demonstrated anti‐inflammatory and proangiogenic effects and improved ischemic muscle regeneration. In this work, these MSC‐derived bioactive factors were loaded into a hydrogel foam to harness immunomodulatory and angiogenic properties from MSC components to facilitate chronic wound healing without the high cost and translational challenges of cell therapies. After incorporation of bioactive factors, the hydrogel foam retained high absorbency, moisture retention, and target water vapor transmission rate. High loading efficiency was confirmed and release studies indicated that over 90% of loaded factors were released within 24 h. Ethylene oxide sterilization and 4‐week storage did not affect the bioactive factor release profile or physical properties of the hydrogel foam dressing. Bioactivity retention of the released factors was also confirmed for as‐sterilized, 4°C‐stored, and −20°C‐stored bioactive hydrogel foams as determined by relevant gene expression levels in treated pro‐inflammatory (M1) macrophages. These results support the use of the bioactive dressings as an off‐the‐shelf product. Overall, this work reports a new method to achieve a first‐line wound dressing with the potential to reduce persistent inflammation and promote angiogenesis in chronic wounds. [ABSTRACT FROM AUTHOR]

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Immunomodulatory agents help maintain a balanced immune system by suppressing excessive immune response or by stimulating the immune system. This study aims to determine the antirheumatoid arthritis and immunomodulatory activities of ethanol extract of Musa paradisiaca L. Var Sapientum peel. Wistar rats were divided into five groups, and induced with rheumatoid arthritis by the intraplantar administration of Complete Freund's Adjuvant (CFA). On day 17 following CFA-induction, the rats were treated as follows; Group 1 (Negative control): sodium carboxymethyl cellulose (1%), Group II (Positive control): diclofenac sodium, Groups III, IV, and V: banana peel extract at doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg, respectively. All treatments were administered orally once daily for 14 days. Paw volume was measured on day 1, 17, and 31. Percentage reduction in paw edema and arthritis index was also measured. Immunomodulatory test was done using delayed-type hypersensitivity which was induced by intraperitoneally and intraplantar administration of 10% sheep red blood cells (SRBC) on 3rd and 7th day. Banana peel extract (100 mg/kg, 300 mg/kg, and 500 mg/kg) was administered orally for 7 days. Paw volume was measured at 4 h (T4), 24 h (T24), and 48 h (T48). Results show that banana peel extract had antirheumatoid arthritis effect. The 100 mg/kg dose was the most effective, with 37.93% reduction in paw edema and an arthritis index of 0.83. In addition, the extract showed activity as immunomodulator at all doses. Therefore, banana peel extract has potential for use as anti-rheumatoid arthritis and immunomodulatory agent. [ABSTRACT FROM AUTHOR]

Abstract Marinobacter nauticus strain GH3 was isolated from the Red Sea, Sharm Elshiekh, and classified according to cultural attributes, biochemical properties, and the analysis of genetic relationships using 16 S rRNA sequences. A substantial proportion of exopolysaccharides (EPS) in GH3-EPS contained a sulfate content of 25.4%, uronic acid (12.18%), and N-acetylglucosamine (13.6%). The composition of monosaccharides in this fraction consists of glucose, glucoronic acid, arabinose, and xylose by 2:4:3:3, respectively. SEM showed a flower-like shape with white bundles on the GH3-EPS surface. GH3-EPS enhancement of the RAW264.7 macrophage line RAW 264.7 ATTC number J774 cell proliferation via MTT assay for cell viability. GH3-EPS had a high stimulation effect on releasing TNF-alpha and IL-10. Followed by its effect against cyclooxygenase (COX-2) and lipoxygenase (LOX), with IC50s of 14.74 and 19.4 µg/ml, respectively. Antioxidant activity was evaluated for GPx-4, GSS, and MDA with highly significant results, and for DPPH, ABTS, and iron chelating with IC50 (43.51, 31.27, and 84.96 µg/ml, respectively). AChE was inhibited by a mean of 52.92 ± 4.54 and 68.22 ± 5.64 µg/ml. In a fish animal model, GH3-EPS demonstrated a positive treatment effect for AD, supporting biochemical studies, histopathology for some brain parts, and toxicity.

Moonerah M Al-Nasser,1 Mashael J Al-Saeedi,2 Saltana A Alhowaiti,2 Zakia Shinwari,3 Fatimah S Alhamlan,2,4 Hani Alothaid,5 Saad Alkahtani,1 Ahmed A Al-Qahtani2,4 1Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; 3Therapeutics & Biomarker Discovery for Clinical Applications, Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 4Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 5Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi ArabiaCorrespondence: Ahmed A Al-Qahtani, Email aqahtani@kfshrc.edu.saIntroduction: Methotrexate (MTX) is a widely used anti-metabolite drug in cancer therapy, but its efficacy is often hindered by reactive oxygen species (ROS)-induced cellular toxicity. Resveratrol, a natural polyphenol, possesses antioxidant and anticancer properties. Therefore, this in vitro study aimed to investigate the synergistic anti-proliferative and anti-inflammatory effects of MTX and resveratrol in human THP-1 cells.Methods: THP-1 cells were differentiated into macrophage-like cells using phorbol 12-myristate 13-acetate. In vitro experiments assessed the impact of various concentrations of MTX and resveratrol on cell viability and proliferation using the MTT assay. Concentration-effect curves were generated to elucidate their relationship. Gene expression was analyzed by RT-qPCR, while chemokine expression was measured via ELISA. Phagocytic and migratory activities were also evaluated.Results: Differentiated THP-1 cells were treated with MTX and resveratrol and stimulated with dimethyl sulfoxide (DMSO) and lipopolysaccharide (LPS) as inflammatory stimuli. The combination of MTX and resveratrol exhibited an anti-proliferative effect in THP-1 cells (p = 0.03). The concentration-effect curve revealed IC50 values of 49.15 μg at 24 hours (R = 0.8236) and 2.029e-005 μg at 48 hours (R = 0.97) for MTX, and 20.17 μg at 48 hours (R = 1.000) and 55.38 μg at 96 hours (R = 0.9666) for resveratrol. Co-treatment with MTX and resveratrol significantly reduced mRNA and chemokine expression of CCL2, CCL3, CCL4, CCL5, and CXCL10 (p < 0.05). Moreover, decreased phagocytic and migratory activities were confirmed by phagocytosis and migration assays (p < 0.05).Conclusion: The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.Keywords: immunomodulatory, immune cells, anti-inflammatory, THP-1, methotrexate, resveratrol

Objective: To evaluate the immunomodulatory function and safety of compound preparation containing Ganoderma lucidum polysaccharides. Methods: According to the Technical Standards for Testing and Assessment of Health Food (2003 Edition), the immunomodulatory function of compound preparation containing Ganoderma lucidum polysaccharides was evaluated comprehensively from cellular immunity, humoral immunity and non-specific immunity by measuring the ability of lymphocyte proliferation, degree of ear swelling, number of hemolytic plaques, phagocytic percentage, phagocytic index and natural killer (NK) cells activity in normal mice. Its safety was evaluated comprehensively by acute oral toxicity test in mice, Ames test and 30 d feeding test in rats. Results: In cellular immunity test, the tested substance had no significant effect on lymphocyte proliferation induced by concanavalin A and degree of ear swelling (P>0.05). In the humoral immunity test, the low dose group (0.17 g/kg), the middle dose group (0.33 g/kg) and the high dose group (1.00 g/kg) could increase the level of antibody-producing cells by 10.98%, 12.08%, 17.63% (P0.05), and no obvious pathological changes were found by histological examination. Conclusion: Compound preparation containing Ganoderma lucidum polysaccharides had a positive effect on immunomodulatory function in mice, and it had a good safety as a health food.

Abstract Background Lactiplantibacillus species are extensively studied for their ability to regulate host immune responses and functional therapeutic potentials. Nevertheless, there is a lack of understanding on the mechanisms of interactions with the hosts during immunoregulatory activities. Methods Two Lactiplantibacillus plantarum strains MKMB01 and MKMB02 were tested for probiotic potential following Indian Council of Medical Research (ICMR) guidelines. Human colorectal adenocarcinoma cells such as HT-29, caco-2, and human monocytic cell THP-1 were also used to study the potential of MKMB01 and MKMB02 in regulating the host immune response when challenged with enteric pathogen Salmonella enterica typhimurium. Cells were pre-treated with MKMB01 and MKMB02 for 4 h and then stimulated with Salmonella. qRT-PCR and ELISA were used to analyze the genes and protein expression. Confocal microscopy and field emission scanning electron microscopy (FESEM) were used to visualize the effects. An Agilent Seahorse XF analyzer was used to determine real-time mitochondrial functioning. Results Both probiotic strains could defend against Salmonella by maintaining gut integrity via expressing tight junction proteins (TJPs), MUC-2, and toll-like receptors (TLRs) negative regulators such as single Ig IL-1-related receptor (SIGIRR), toll-interacting protein (Tollip), interleukin-1 receptor-associated kinase (IRAK)-M, A20, and anti-inflammatory transforming growth factor-β and interleukin-10. Both strains also downregulated the expression of pro-inflammatory cytokines/chemokines interleukin-1β, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor-alpha (TNF-α), interleukin 6, and nitric oxide (NO). Moreover, TNF-α sheddase protein, a disintegrin and metalloproteinase domain 17 (ADAM17), and its regulator iRhom2 were downregulated by both strains. Moreover, the bacteria also ameliorated Salmonella-induced mitochondrial dysfunction by restoring bioenergetic profiles, such as non-mitochondrial respiration, spare respiratory capacity (SRC), basal respiration, adenosine triphosphate (ATP) production, and maximal respiration. Conclusions MKMB01 and MKMB02 can reduce pathogen-induced gut-associated disorders and therefore should be further explored for their probiotic potential.

In this study, oligosaccharide from Caulerpa racemosa var. peltate (CRVO-G) was prepared by sequential enzymatic hydrolysis with lactase, membrane filtration, dialysis, and freeze-drying, and the relative molecular mass and monosaccharide composition of CRVO-G were measured. Meanwhile, the immunoregulatory activity of CRVO-G was evaluated and its mechanism of action was studied. The results showed that CRVO-G was a mixture of two tetrasaccharides and one hexasaccharide with relative molecular masses of 617.115, 621.081, and 995.368, and was mainly composed of galactose (51.0%), mannose (21.3%), glucose (11.5%), xylose (6.5%), rhamnose (2.3%), glucuronic acid (2.0%), glucosamine hydrochloride (1.8%), fucose (0.8%), glucosamine hydrochloride (0.7%), galacturonic acid (0.7%), mannuronic acid (0.7%), and arabinose (0.6%). In addition, CRVO-G had good immunomodulatory activity, as manifested by increased release of nitric oxide and cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α). The results of metabolomics analysis and Western blot showed that CRVO-G could promote the synthesis of thromboxane A2 (TXA2) and 15-keto prostaglandin F2α (15-keto-PGF2α) in the arachidonic acid pathway of macrophages, and increase the expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the phosphorylation of nuclear factor κB (NF-κB). In summary, CRVO-G exerts immunomodulatory effects by the NF-κB/iNOS/COX-2 pathway in RAW264.7 macrophages.

Background: Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. Infection with virulent strains of T. gondii induces excessive production of pro-inflammatory cytokines and increases fatality. Propolis has potential as an anti-inflammatory and immunomodulator. Aim: This study aimed to evaluate the pro-inflammatory cytokines response of Interleukin-2 (IL-2) and IL-17, and the anti-inflammatory cytokine IL-10 in mice infected with T. gondii RH strain and treated with ethanol extract of Trigona bee propolis (EEP) from Lombok, West Nusa Tenggara (NTB), Indonesia. Methods: A total of 36 mice were divided into six groups with six mice per group. Group 1 was considered as a negative control; mice were not infected and not treated while in groups 2 to 6, mice were infected with 100 T. gondii (tachyzoites). Mice in group 2 were infected but not treated whereas in groups 3, 4, 5 and 6, respectively, were treated orally with Cotrimoxazole 40 mg/kg body weight, EEP 1 mg, EEP 2 mg and EEP 4 mg, the day after infection for 3 days. All mice under study were euthanized following ethical considerations with prior approvals, on the fifth day post-infection and spleens were taken to observe cytokines using flow cytometry. Statistical analysis was performed with one-way ANOVA and Duncan Multiple Range Test using (you may add any statistical tool/ software if used?? Like R version? , SPSS, version? If you used any of these/others) Results: EEP (1-4 mg) increased CD4+ T cells, CD8+ T cells, and CD11b+ cells in infected mice, though not significantly (p>0.05), unlike cotrimoxazole, which showed significant increases (p [Open Vet J 2024; 14(9.000): 2280-2286]

Abstract Background Mesenchymal stem cells (MSCs) have shown a positive effect on Osteoarthritis (OA), but the efficacy is still not significant in clinical. Conventional two-dimensional (2D) monolayer culture method is prone to cause MSCs undergoing replication senescence, which may affect the functions of MSCs. Three-dimensional (3D) culture strategy can sustain cell proliferative capacity and multi-differentiation potential. This study aimed to investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) cultured by 3D hanging drop method on OA. Methods hUC-MSCs were isolated from umbilical cord and cultured by 3D hanging drop method for 48 h. Scanning electron microscopy (SEM) was used to observe gross morphology 2D and 3D hUC-MSCs. Transcriptome comparison of gene expression differences between 2D and 3D hUC-MSCs. GO enrichment analysis, KEGG pathway enrichment analysis and GSEA enrichment analysis were used to analyze the impact of 3D hanging drop culture on the biological functions of hUC-MSCs. Female New Zealand rabbits (n = 12) were divided into 4 groups: Normal group, Model group, 2D hUC-MSCs treatment group and 3D hUC-MSCs treatment group. After 8 weeks, the gross and histological appearance of the cartilage was evaluated by safranin O-fast green staining and Mankin scoring system. The expression of type I collagen and type II collagen was detected by immunohistochemistry. The levels of IL-6, IL-7, TNFα, TGFβ1 and IL-10 in the knee joint fluid were tested by ELISA. Results 3D hanging drop culture changed cell morphology but did not affect phenotype. The MSCs transcriptome profiles showed that 3D hanging drop culture method enhanced cell-cell contact, improved cell responsiveness to external stimuli and immunomodulatory function. The animal experiment results showed that hUC-MSCs could promote cartilage regeneration compared with Model group. 3D hUC-MSCs treatment group had a higher histological score and significantly increased type II collagen secretion. In addition, 3D hUC-MSCs treatment group increased the expression of anti-inflammatory factors TGFβ1 and IL-10. Conclusion The above experimental results illustrated that 3D hanging drop culture method could enhance the therapeutic effect of hUC-MSCs, and showed a good clinical application prospect in the treatment of OA.

Abstract Diarrheal diseases remain the leading cause of high mortality among the infants, particularly in the developing countries; Probiotic intervention for diarrhea has been an ongoing novel approach to diarrheal prevention and treatment. This study aims to characterize immunogenic and probiotic properties of lactic acid bacteria (LAB) isolated from human breast milk and neonates’ faeces. The LAB isolates from 16 mothers’ breast milk and 13 infants’ faeces were screened and identified by 16 S rRNA gene partial sequencing. Their antimicrobial activities against 5 strains of diarrheagenic Escherichia coli were tested. Organic acids production was quantified by HPLC, and antibiotic resistance pattern were determined by VITEK®. Autoaggregation, co-aggregation and hydrophobicity properties were assessed by UV spectrophotometry and immunomodulatory effect was determined in mouse model. Ninety-three LAB of five genera were identified. The most abundant species was Lactiplantibacillus plantarum with inhibition zones ranged from 8.0 to 25.0 ± 1 mm. Lacticaseibacillus rhamnosus A012 had 76.8 mg/mL lactic acid, (the highest concentration), was susceptible to all antibiotics tested. L. plantarum A011 and L. rhamnosus A012 were highly resistance to gastrointestinal conditions. L. rhamnosus A012 produced hydrophobicity of 25.01% (n-hexadecane), 15.4% (xylene) and its autoaggregation was 32.52%. L. rhamnosus A012 and L. plantarum A011 exert immunomodulatory effects on the cyclophosphamide-treated mice by upregulating anti-inflammatory cytokine and downregulating proinflammatory cytokines. Lactobacillus sp. demonstrated good probiotic and immunomodulatory properties. Further works are ongoing on the practical use of the strains.

Abstract Mesenchymal stem/stromal cells (MSCs) have emerged as a promising tool in the field of regenerative medicine due to their unique therapeutic properties as they can differentiate into multiple cell types and exert paracrine effects. However, despite encouraging results obtained in preclinical studies, clinical trials have not achieved the same levels of efficacy. To improve the therapeutic properties of MSCs, several strategies have been explored. Therefore, in this review, the therapeutic properties of MSCs will be analyzed, and an update and overview of the most prominent approaches used to enhance their therapeutic capabilities will be provided. These approaches include using drugs, molecules, strategies based on biomaterials, and modification parameters in culture. The strategy described shows several common factors among those affected by these strategies that lead to an enhancement of the MSCs therapeutic properties such as the activation of the PI3K/AKT pathway and the increased expression of Heat Shock Proteins and Hypoxia-Inducible Factor. The combined effect of these elements shift MSCs towards a glycolytic state, suggesting this shift is essential for their enhancement. Graphical abstract

Abstract Background This meta-analysis aimed to summarize the immunomodulatory effect of Huaier (Trametes robiniophila Murr) granule as adjuvant therapy in patients with cancer. Materials and methods Two authors conducted a search for literature indexed on various databases including PubMed, Embase, Cochrane Library, CNKI, Sinomed, VIP, and WanFang. Randomized controlled trials (RCTs) that investigated the immunomodulatory effect of Huaier granule as adjuvant therapy in cancer patients were included. The outcome of interest included T-lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+/CD8+), immunoglobulin (IgA, IgG, IgM), and natural killer (NK) cells. Results We identified 29 RCTs involving a total of 2206 cancer (including hepatocellular, breast, gastric, colorectal, lung, or nasopharyngeal carcinoma) patients. Compared with conventional treatment alone, Huaier combined conventional treatment significantly improved CD3+ (mean difference [MD] 6.95; 95% confidence intervals [CI] 4.42–9.48), CD4+ (MD 5.53; 95%CI 4.22–6.83), CD4+/CD8+ (MD 0.35; 95%CI 0.25–0.45), IgA (standardized mean difference [SMD] 1.18; 95%CI 0.44–1.93), IgG(SMD 1.71; 95%CI 1.11–2.30), IgM (SMD 0.83; 95%CI 0.59–1.07), and NK cells (MD 5.01; 95%CI 3.61–6.40). However, the effect of Huaier on CD8+ (MD − 1.35; 95%CI − 2.80 to 0.11) was not statistically significant between the groups. Conclusions Huaier granule as adjuvant therapy may significantly improve immune function in patients with cancers. However, additional well-designed RCTs are needed to validate the current findings considering the methodological flaws of the analyzed trials.

Functional foods optimize the immune system and prevent diseases which can lead to stress. In this work, authors investigated the immunomodulatory properties of bambara groundnut condiment extract, using leucocytes of diarrhoeal rats as probe. Wistar rats were sorted and divided into 5 groups by weight (n = 5). Rats were induced for diarrhoea using castor oil. Diarrhoeal rats were then treated as follows: Group 1 received 2.5 mg levamisole per kg body weight, groups 2, 3 and 4, received 100, 250, 500 mg of bambara groundnut condiment extract (BGCE) per kg body weight respectively; group 5 received 2.5 ml of 3% tween 80 per kg body weight. Following standard protocols, treated rats were assessed for immunoglobulins G and M, leucocyte mobilization, as well as primary and secondary antibody titre values. Attempt was also made to screen bambara groundnut condiment for phytochemicals, both qualitatively and quantitatively, following standard protocols. Obtained data were analysed by SPSS (version 20). Values were expressed as Mean ± S.E.M. Mean values were evaluated by one way analysis of variance (ANOVA) and means were separated by Duncan’s multiple range test (DMRT). Differences were considered significant at p < 0.05. Alkaloids, Phenols, Saponin and Flavonoids were among phytochemicals found in bamabara groundnut condiment in appreciable amount. Anthraquinones, Cardenolides and Chalcones were not detected. Quantitatively, the most abundant phytochemicals in bamabara groundnut condiment were alkaloids (0.68 %), saponin (0.29 %) cardiac glycoside (0.14 %), Phenols (0.13 %). The most mobilized leucocytes were the neutrophils which ranged between 6.83 x 103 µl in group 1 and 13.10 x 103 µl in group 5. Plasma concentrations of immunoglobulin G (2.22–2.63 g/l) were higher than values for immunoglobulin M (0.30–0.49 g/l) across all groups. Furthermore, secondary antibody titre values were generally higher than values of primary antibody titre values (19.20 vs 16.00 in group 1, and 25.60 vs 32.00 in group 4), for secondary and primary antibody titre values respectively. Bambara groundnut condiment extract was found to have immunostimulatory properties, obtained from the array of phytochemicals it possesses.

Ulcerative colitis (UC) is an idiopathic, chronic, relapsing inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. The pathophysiology of UC is complicated and involves several factors including immune, genetic, and environmental factors. Recently, a huge amount of research has concentrated on the role of interleukins including interleukin-6 (IL-6) in its pathophysiology. Thus, this study aims to examine the colo-protective and immunomodulatory effect of Tocilizumab (TCZ) in an experimental model of dextran sulfate sodium (DSS) induced UC. In the current study, we analyzed the inflammatory, immunomodulatory, apoptotic, autophagy, and endoplasmic reticulum (ER) stress markers and other clinical features including stool consistency, rectal bleeding, and edema markers in rats. Our results showed that induction of colitis caused bloody diarrhea and increased IL-6 levels. Treatment with TCZ significantly ameliorated DSS-induced injury via decreasing inflammatory markers of colon injury (IL-6), signal transducer and activator of transcription-3 (STAT-3), and C-reactive protein (CRP). Furthermore, TCZ attenuated the apoptotic marker (caspase-3), and down-regulated endoplasmic reticulum stress sensor proteins (inositol- requiring transmembrane kinase endonuclease-1 (IRE-1) and activated transcription factor-6 (ATF-6)) and autophagy proteins (autophagy-related 16-like protein 1 (ATG16L1) and nucleotide-binding oligomerization domain-containing protein-2 (NOD2)), as compared to DSS group. Altogether, the current data suggest TCZ to be a promising protective therapy against UC. [ABSTRACT FROM AUTHOR]

Xiawan Yang,1– 3,&ast; Yingying Shen,1– 3,&ast; Tonglin Hu,1– 3 Hangchao Li,1– 3 Yun Zhang,1– 3 Yiping Shen,1– 3 Dijiong Wu1– 4 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dijiong Wu; Yiping Shen, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Youdian Road No. 54, Hangzhou, 310006, Zhejiang, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn; shenyp_@126.comBackground: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens.Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission.Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation.Keywords: carrimycin, perianal infection, acute myeloid leukemia, immunomodulatory

Taiyu Song,&ast; Lulu Yao,&ast; Angang Zhu,&ast; Guangling Liu, Beibei Zhu, Qian Zhao, Yue Zhao, Jinya Wang Department of Pediatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinya Wang, Email jinyawang@vip.163.comIntroduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma.Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining.Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg).Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.Keywords: asthma, cathepsin B, bioactive peptide nanocarrier, MPP-Trp, immunomodulatory

Fatty muscle degeneration and muscle atrophy have not been successfully treated due to their irreversible pathology. This study evaluated the efficacy of rat adipose-derived mesenchymal stem/stromal cells (ADP MSCs) in treating fatty muscle degeneration (FD). A total of 36 rats were divided into three groups: the control (C) group (n = 12); FD model group, generated by sciatic nerve crushing (n = 12); and the group receiving ADP MSC treatment for FD (FD+MSCs) (n = 12). In Group FD+MSCs, ADP MSCs were injected locally into the gastrocnemius muscle one week after the FD model was created (Day 8). On Day 22 (n = 18) and Day 43 (n = 18), muscle morphology, histopathology, and molecular analyses (inflammation, muscle atrophy, adipocytes, and muscle differentiation markers) were performed. In Group FD+MSCs, the formation of immature myofibers was observed on Day 22, and mitigation of fatty degeneration and muscle atrophy progression was evident on Day 43. Gene expression of muscle atrophy markers (FBXO32, TRIM63, and FOXO1) and adipogenic markers (ADIPOQ, PPARG, FABP4, and PDGFRA) was lower in Group FD+MSCs than Group FD on Day 43. ADP MSCs induce anti-inflammatory effects, inhibit fat accumulation, and promote muscle regeneration, highlighting their potential as promising therapy for FD and atrophy.

Abstract Background Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. Hypothesis Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. Animals Fifty‐one dogs with mast cell tumors (MCTs). Materials and Methods Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine‐2‐receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre‐ and post‐treatment time points, and between pre‐ and post‐time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. Results Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre‐ to post‐treatment (3.429; range, 1.417–15 to 5.631; range, 2.654–92; P

Objective: To compare the regulatory effects of adlay (Coix lachryma-jobi L.) seeds fermented and not fermented by Lactobacillus plantarum NCU137 on immune and intestinal mucosal barrier function in mice induced by cyclophosphamide (CTX). Methods: BALB/c mice were randomly divided into four groups, including normal, CTX-induced model, non-fermented adlay seed (NFC) and fermented adlay seed (FC) treatment. The mice in the normal and CTX groups were orally administrated with 0.2 mL of physiological saline for 10 days, while those in the NFC and FC groups 0.2 mL of non-fermented and fermented adlay seeds for 10 days, respectively. The immunosuppressed mouse model was established by daily intraperitoneal injection of 100 mg/kg of CTX for the last three days of the administration period, while the normal group was intraperitoneally injected with the same volume of normal saline. Spleen index, the number of spleen T lymphocyte subsets, and the levels of cytokines and immunoglobulin were measured, histopathological examination of the small intestine was performed and intestinal mucosal barrier function was detected. Results: Compared with the CTX group, fermented adlay seeds significantly increased the spleen and thymus indexes of immunosuppressed mice, up-regulated the cluster of differentiation (CD) 4+/CD8+ ratio of spleen T lymphocytes, down-regulated the levels of spleen pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), and increased serum immunoglobulin (Ig) M and IgG levels. Moreover, fermented adlay seeds repaired small intestinal mucosal structure and up-regulated the gene expression of occludin and E-cadherin, and the effect was more pronounced than that of non-fermented adlay seeds. Conclusion: Coix lachryma-jobi L. seeds fermented by L. plantarum NCU137 have the potential to regulate immune and intestinal mucosal barrier function, which are expected to be developed into a novel health food with immunomodulatory function.

Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely match natural bone regeneration processes in vivo. In this study, a novel biomimetic coating on titanium substrates (DPA‐Co/GFO) through a mussel adhesion‐mediated ion coordination and molecular clicking strategy is engineered. In vivo and in vitro results confirm that the coating exhibits excellent biocompatibility and effectively promotes angiogenesis and osteogenesis. Crucially, the biomimetic coating targets the integrin α2β1 receptor to promote M2 macrophage polarization and achieves a synergistic effect between immunomodulation and vascularized bone regeneration, thereby maximizing osseointegration at the interface. Mechanical push‐out tests reveal that the pull‐out strength in the DPA‐Co/GFO group is markedly greater than that in the control group (79.04 ± 3.20 N vs 31.47 ± 1.87 N, P < 0.01) and even surpasses that in the sham group (79.04 ± 3.20 N vs 63.09 ± 8.52 N, P < 0.01). In summary, the novel biomimetic coating developed in this study precisely matches the natural process of bone regeneration in vivo, enhancing interface‐related osseointegration and showing considerable potential for clinical translation and applications. [ABSTRACT FROM AUTHOR]

Introduction: The therapeutic efficacy of mesenchymal stromal cells (MSCs) in inflammatory bowel disease is not completely known and is not consistent. Priming with inflammatory cytokines has been proposed to adapt MSCs to an inflammatory environment to have them ready to counteract it, but may have undesirable effects on MSCs, such as increased immunogenicity. In this study, we hypothesized that priming MSCs with inflamed intestinal tissue would more effectively enhance their therapeutic effect on intestinal inflammation. Methods: The capacity of canine adipose-derived MSCs (cADSCs) primed with colon tissue homogenates from mice with experimentally induced colitis or a combination of tumor necrosis factor-a and interferon-g to inhibit T-cell proliferation was analyzed, along with their own apoptosis, proliferation, cell surface marker expression, and transcriptome. In addition, colitis mice were treated with the primed cADSCs to assess colitis severity and immune cell profile. Results: Priming with cytokines induced apoptosis, decreased cell proliferation, and major histocompatibility complex-II gene expression in cADSCs, but these adverse effects were mild or absent with colitis-tissue priming. cADSCs primed with colitis tissue reduced the severity of colitis via the induction of M2 macrophages and T-regulatory cells and suppression of T-helper (Th)1/Th17-cell responses, and their effects were comparable to those of cytokine-primed cells. Discussion: Our results emphasize the importance of the activation of MSCs by the appropriate microenvironment to maximize their therapeutic effect. [ABSTRACT FROM AUTHOR]

Background: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. Methods: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. Results: Recent findings indicate that various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. Conclusion: This article demonstrates the significance and progress of ncRNAs in children's AR. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore. [ABSTRACT FROM AUTHOR]

Immune dysregulation is a pivotal factor in the onset and progression of various diseases. In cancer, the immune system's inability to discern and eliminate abnormal cells leads to uncontrolled tumor growth. When faced with resilient pathogens or harmful toxins, the immune system encounters challenges in clearance and neutralization. Achieving a delicate balance of pro‐inflammatory and anti‐inflammatory signals is essential in managing a range of disorders and diseases. Like in other biomedical research domains, nanotechnology has provided innovative approaches for rebalancing host immunity. Among the plethora of nanotechnology‐based interventions, the concept of cell membrane‐coated nanoparticles holds significant potential for immunomodulatory applications owing to their biomimetic properties that allow for precise interaction with the compromised immune system. This review thoroughly examines the potential of novel nanosystems for immune modulation. The exploration covers crucial elements, including the origins and characteristics of cell membranes, the methods employed for their procurement and coating, physicochemical/biological characterization techniques, and enhancement of their therapeutic efficacy via functionalization. Subsequently, case studies‐based analysis of utilizing these bioinspired nanosystems in tackling different conditions caused by immune disturbance has been comprehensively discussed. [ABSTRACT FROM AUTHOR]

Immune response is pivotal in the secondary injury of spinal cord injury (SCI). Polarization of macrophages (MΦ) influences the immune response in the secondary injury, which is regulated by several immune-related proteins. M2Φ plays the immunomodulatory role in the central nervous system. This study used bioinformatic analysis and machine algorithms to screen hub immune-related proteins after SCI and experimentally investigate the role of the target protein in the M2Φ polarization and immunomodulation in rats and in vitro after SCI. We downloaded GSE151371 and GSE45006, hub immune-related genes were screened using machine learning algorithms, and the expression of S100A9 was verified by datasets. Allen's weight-drop injury SCI model in Sprague–Dawley rat and bone marrow-derived rat MΦ with myelin debris model were used to study the effects of S100A9 on M2Φ polarization and immunomodulation at the lesion site and in vitro. Bioinformatic analysis showed that S100A9 acts as a hub immune-related gene in the SCI patients and rats. S100A9 increased at the lesion site in SCI rats, and its inhibition reduced CD206 and ARG-1 expression. Exogenous S100A9 promoted CD206 and ARG-1 expression in MΦ. S100A9 also increased the expression of PD-L1 and decreased MHC II at the lesion site in SCI rats and MΦ with myelin debris, and enhanced mitochondrial activity in rat MΦ with myelin debris. In conclusion, S100A9 is an indispensable factor in the immune process in secondary injury following SCI. [ABSTRACT FROM AUTHOR]

The sequential culture expansion has been shown to affect the favorable characteristics of human mesenchymal stem/stromal cells (hMSCs), including their immunomodulatory potential. Hereby, we have investigated the immunomodulatory potential of Yazd human testicular Cells (YhTCs) regarding gene expression profile assessment during their lifespan. Morphological examination, immunostaining of vimentin and fibronectin markers, and flow cytometry analysis were used to confirm cultured cells' MSC properties. Quantitative RT-PCR was used to investigate the target genes, COX-1, TGF-β, IL-6, VCAM-1, and FAS, at different passage numbers (P3, P6, and P9). Our findings confirmed the MSC properties of YhTCs over the lifespan. The results of COX-1 and IL-6 indicated significantly higher expression levels at the late passages (p‑value = 0.03 and p-value = 0.01, respectively). Despite the similar expression pattern, VCAM-1 expression altered significantly at different passages (p-value = 0.0006), but the changes in TGF-β expression levels were non-significant across the lifespan. The YhTCs maintained the main characteristics of MSCs over the sequential culture expansion. Although some of the target genes in the study were sensitive to the culture expansion in the unstimulated YhTCs (IL-6, COX-1, and VCAM1), it seems that FAS and TGF-β need external stimuli or intracellular signals to be induced in YhTCs. [ABSTRACT FROM AUTHOR]

Bioactive peptides are short chains of amino acids with specific biological activities, sourced from proteins in various natural sources such as food, animal tissues, and microbial cultures. They offer potential health benefits including antioxidant, antihypertensive, antimicrobial, and immunomodulatory activities. Researchers are exploring their potential applications in medicine alternatives to pharmaceutical drugs and antibiotics, as well as in the food industry as substitutes for synthetic additives. Bioactive peptides can be derived from a diverse array of natural sources including milk, eggs, fish, plants, and microbial proteins, making them a promising area of research. In poultry nutrition, bioactive peptides have demonstrated remarkable benefits. They exhibit antimicrobial activity, which contributes to better gut health and reduced risk of infections. Additionally, they can enhance growth performance by improving nutrient absorption and utilization, and may play a role in alleviating stress in poultry, leading to improved overall health and performance. Various studies have highlighted the positive effects of bioactive peptides derived from different sources such as soybean, cottonseed, and canola meal on broiler growth, feed conversion ratio, and health indicators. The potential of bioactive peptides as functional nutrients in poultry nutrition and health management is indeed promising. [ABSTRACT FROM AUTHOR]

Urtica dioica (stinging nettle) has been in feed in the past in many countries, and mainly, its leaves were used as a food source for birds and animals to enhance productivity and accelerate their metabolism. It also enhances the carcass percentage of meat animals, particularly broilers. It can potentially be used as a soya bean replacer as it will lower the feed cost. Its leaves can boost the immune system, particularly enhancing the chicken's ability to fight against gram-positive and gram-negative bacteria. Its antioxidant capability prevents free radical generation, reducing the chances of free radicle injuries. In ruminants, its use as a feed additive can lead to an increase in milk production. In animals, any kind of stress during the raising stage deteriorates the meat quality, so this herb prevents the carcass meat from deteriorating and has a better percentage of crude protein, crude fiber, and metabolizable energy, which results in an economic perspective. Supplementation of Urtica dioica in feed can enhance carcass output and provide the potential to counteract bacterial and viral diseases. [ABSTRACT FROM AUTHOR]

Background: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. Hypothesis: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. Animals: Fifty‐one dogs with mast cell tumors (MCTs). Materials and Methods: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine‐2‐receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre‐ and post‐treatment time points, and between pre‐ and post‐time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. Results: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre‐ to post‐treatment (3.429; range, 1.417–15 to 5.631; range, 2.654–92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. Conclusions: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs. [ABSTRACT FROM AUTHOR]

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Introduction: In recent years, diverse initiatives have been carried out to control the COVID-19 pandemic, ranging from measures restricting social activities to analyzing drugs and vaccines. Studies on herbal medicines are also increasingly conducted in various countries as an adjuvant therapy or supplement. Therefore, this systematic review aimed to investigate the efficacy of herbal medicines analyzed from various countries through clinical trials with the randomized controlled trial method. The outcomes of Length of Stay (LOS), Negative Conversion Time (NCT), and Negative Conversion Rate (NCR) were the main focus. Methods: An extensive review of literature spanning from 2019 to 2023 was carried out using well-known databases including PubMed, Scopus, and Cochrane. The search included relevant keywords such as "randomized controlled trial," "COVID-19," and "herbal medicine." Results: A total of 8 articles were part of the inclusion criteria with outcomes of LOS, NCT, and NCR. In terms of LOS outcomes, all types of herbal medicines showed significant results, such as Persian Medicine Herbal (PM Herbal), Persian Barley Water (PBW), Jingyin Granules (JY granules), Reduning Injection, and Phyllanthus emblica (Amla). However, only JY granules showed significant results in NCR outcome, while JY granules and Reduning Injection showed significant results in reducing NCT. Conclusion: These findings enrich our understanding of the potential benefits of herbal medicines in influencing LOS, NCR and NCT parameters in COVID-19 patients. Herbal medicines worked to treat COVID-19 through antiviral, antiinflammatory, and immunomodulatory mechanisms. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have emerged as a promising approach for drug delivery strategies because of their unique properties. These strategies include stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, immunomodulatory effects, stem cell-laden scaffolds, and scaffold-free stem cell sheets. MSCs offer advantages such as low immunogenicity, homing ability, and tumor tropism, making them ideal for targeted drug delivery systems. Stem cell-derived extracellular vesicles have gained attention for their immune properties and tumor-homing abilities, presenting a potential solution for drug delivery challenges. The relationship between MSC-based drug delivery and the self-renewal and differentiation capabilities of MSCs lies in the potential of engineered MSCs to serve as effective carriers for therapeutic agents while maintaining their intrinsic properties. MSCs exhibit potent immunosuppressive functions in MSC-based drug delivery strategies. Stem cell-derived EVs have low immunogenicity and strong therapeutic potential for tissue repair and regeneration. Scaffold-free stem cell sheets represent a cutting-edge approach in regenerative medicine, offering a versatile platform for tissue engineering and regeneration across different medical specialties. MSCs have shown great potential for clinical applications in regenerative medicine because of their ability to differentiate into various cell types, secrete bioactive factors, and modulate immune responses. Researchers are exploring these innovative approaches to enhance drug delivery efficiency and effectiveness in treating various diseases. [ABSTRACT FROM AUTHOR]