The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

Anti-leishmanial,immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major

Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.

Pulmonary cryptococcosis after immunomodulator treatment in patients with Crohn’s disease:Three case reports

BACKGROUND Corticosteroids and anti-tumor necrosis factorαmAbs are widely used to treat Crohn's disease(CD).However,one disadvantage of this treatment is impairment of normal immune function,leading to an increased risk of infection.Cryptococcus infection is an opportunistic infection that occurs mainly in immunocompromised patients and poses a significant diagnostic challenge in patients with CD.CASE SUMMARY Here,we report three cases of pulmonary cryptococcosis in patients with CD after receiving immunomodulatory treatment.The patients presented with no or mild respiratory symptoms.Chest computed tomography scans revealed pulmonary nodules in the unilateral or bilateral lobes.Diagnoses were made using pathological examination and metagenomic sequencing.The patients were treated with fluconazole 400 mg once daily for 1 to 6 mo,and symptoms were resolved.Literature searches were conducted in PubMed,Web of Science,and Embase to retrieve previously reported cases and summarize patient characteristics.CONCLUSION The incidence of cryptococcus infection has increased along with immunomodulator use.Clinical vigilance is required for early identification and standardized treatment.

The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production

Host defense peptides(HDPs)are small molecules with broad-spectrum antimicrobial activities against infectious bacteria,viruses,and fungi.Increasing evidence suggests that HDPs can also indirectly protect hosts by modulating their immune responses.Due to these dual roles,HDPs have been considered one of the most promising antibiotic substitutes to improve growth performance,intestinal health,and immunity in farm animals.This review describes the antimicrobial and immunomodulatory roles of host defense peptides and their recent applications in animal production.

Immunomodulatory effect of ethanol-soluble polypeptides from Atlantic cod (Gadus morhua)

There are many active substances in Atlantic cod(Gadus morhua)explaining the variety of biological activities.In order to study the immunomodulatory activity and the mechanism of Atlantic cod peptides at the cellular level.In this study,cod peptides were isolated by 80%ethanol extraction method,the isolated ethanol-soluble cod peptides(CP-ES)were investigated and their immunomodulatory activity was verified.Additionally,CP-ES showed lower molecular weight and more hydrophobic amino acids.CP-ES could promote the proliferation of spleen lymphocytes and T lymphocytes in mice,suggesting that CP-ES may regulate adaptive immunity.It promoted the release of NO and the expression of iNOS,TNF-α,IL-6 and IL-1βgenes in macrophages,suggesting that CP-ES may regulate innate immunity.CP-ES could promote the expression of TLR2 gene,and the peptides identified in CP-ES were docked with TLR2 to predict the peptides playing a major role in CP-ES.These results suggested that CP-ES may regulate the immune activity of both innate and adaptive lines.

The immunomodulatory effects of bone marrow-derived mesenchymal stem cells on lymphocyte in spleens of aging rats

Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.

Immunomodulatory activity of butanol fraction of Gentiana olivieri Griseb. on Balb/C mice

Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodulation such as the humoral antibody response(hemoglutination antibody titres), cell mediated immune response(delayed type hypersensitivity and in vivocarbon clearance or phagocytosis). Ethanol(80%) extract of flowering aerial parts of G.olivieriand its butanol fraction were administered p.o.(orally) to the mice. Levamisole, 2.5 mg/kg was used as standard drug.Results:There was a potentiation of immune response to sheep red blood cells by cellular and humoral mediated mechanisms comparable to levamisole(2.5 mg/kg) by both 80% ethanol extract and the butanol fraction at doses of 50-200 mg/kg in male Balb/C mice. Both significantly(P<0.01) potentiated the humoral immune response in cyclophosphamide(250 mg/kg)immunosupressed mice at 100 and 200 mg/kg of each extract and fraction as compared to control.The potentiation of delayed type hypersensitivity response was statistically significant(P<0.01) at200 mg/kg of ethanol extract and 100, 200 mg/kg of butanol fraction as compared to control. The phagocytosis was significant at 200 mg/kg with butanol fraction ofG. olivieri.Conclusions:The results reveal the immunostimulant effects of plantG. olivieriin mice by acting through cellular and humoral immunity in experimental models of immunity in mice. Butanol fraction is the most effective at a dose level of 200 mg/kg.

CLINICAL APPLICATION OF CHINESE HERBS REMEDIES AS IMMUNOMODULATORS IN THE TREATMENT OF CANCER

IMMUNITY AND TUMOR Immune system has closely relation to the growth and development of tumor. One of its immune functions is to constantly recognize and kill malignant cells which develop from normal cells. The occurance of tumor indicates to some extent the failure of this "immune serveillance" function. Many studies have shown that the tumor cells of body have some tumor interrelative antigen that dose not exist in normal tissues. Tests in vitro

Evaluation of Immunomodulatory Activity of the Herbals Formula Viranur, Turmeric （Curcuma heyneana Val.） and Phyllanthus （Phyllanthus niruri L.） in Layer Chicken Vaccinated with Avian Influenza

The aim of this research was to know the effect of herbal as immunomodulator on chicken layer vaccinated with avian influenza. A total of 60 chickens were alloted into three treatment groups： control group （KA）, group KB and group KC, with 20 chicken each group. All the chickens were vaccinated with Newcastle disease （ND） in the age of one week, and a week later they were vaccinated with avian influenza （AI）. The chickens in group KB were drunken with herbal solution containing of 5 g turmeric （Curcuma heyneana Val.） and 25 g phyllanthus （Phyllanthus niruri L.） and group KC were drunken with herbal solution containing of 36 g the herbals formula Viranur and 25 g phyllanthus （Phyllanthus niruri L.）, respectively for four weeks. Thirty days after AI vaccinated, all of chicken were weighed and necropsied. Samples from bursa of Fabricius, tymus and spleen were taken for weighing and histopathological examination. The weight indexs of bursa of Fabricius, tymus and spleen were not significantly different between control group and treatment group in the considered statistically significance （P 〉 0.05）, but the treatment groups （KB and KC） had higher weight index. The histopathologically changes of spleen in both control group and treatment groups were not different, although in the group KC, in bursa of Fabricius, there was lymphocyte increase in its lymphoid follicles; and in the group KB and KC, the tymus were more widening in the cortex than medulla. The conclusion of this study showed that the herbals can stimulate lymphocyte activity.

Development of New Strategy for Non-Antibiotic Therapy: Bovine Lactoferrin Has a Potent Antimicrobial and Immunomodulator Effects

The antibiotic therapy has many problems, such as antibiotics resistance, hypersensitivity, direct toxicity, antibiotic-induced immunosuppresion and super-infections. This is highlighting the need for a new strategy for non-antibiotic therapy through the use of novel immunomodulators as naturally released ones (Lactoferrin). The present study investigates the potential of bovine lactoferrin (bLf), isolated from bovine milk whey, to prevent Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Streptococcus agalactiae (S. agalactiae) and Pseudomonas aeruginosa (P. aerogenosa) growth and then evaluates its immunomodulator effect. First, bLf isolation was attempted from bovine milk whey using a cation exchange chromatography by SP-Sepharose. Second, the antimicrobial activity assays were trailed to study the antimicrobial activity of bLf. Finally, the immune effect of bLf was studied by lymphocyte transformation test. It was found that bLf was separated around molecular weight of 80 kDa and showed significant inhibitory effect against E. coli followed by P. aeruginosa, S. agalactiae and S. aureus. bLf increased lymphocyte transformations mean values in a dose dependant manner. The highest transformations mean value was determined at 50 μg/mL. In conclusion, these results suggest that bLf is a potent natural antimicrobials and immunomodulator agent.

Development of New Strategy for Non-Antibiotic Therapy: Dromedary Camel Lactoferrin Has a Potent Antimicrobial and Immunomodulator Effects

The human and bovine lactoferrin have been studied extensively, but very few reports have been published concerning camel lactoferrin (cLf). The present study aimed to isolate cLf and evaluate its efficiency including antimicrobial activity and immunomodulator effects. cLf isolation was attempted from camel milk whey using a cation exchange chromatography by SP-Sepharose. The antimicrobial activity of the isolated cLf was investigated against Staphylococcus aureus (S. aureus), Streptococcus agalactiae (S. agalactiae), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aerogenosa) strains. The immune effect of cLf was studied by lymphocyte transformation test. It was found that cLf was separated around molecular weight of 80 kDa and showed significant inhibitory effect against E. coli followed by P. aeruginosa, S. agalactiae and S. aureus. cLf increased lymphocyte transformations mean values in a dose dependant manner. The highest transformations mean value was determined at 50 μg/mL. In conclusion, these results suggest that cLf is a potent natural antimicrobial and novel immunomodulator agent.

A PRELIMINARY STUDY OF THE EFFECTS OF CHEMOTHERAPEUTICAGENTS IN COMBINATION WITH CHINESE HERBAL COMPOUNDS AS IMMUNOMODULATORS IN MOUSE S_(180)

The effect of the Chinese herbal compound (CHC) on solid sarcoma 180 (S180) in Swiss mice was studied either alone or in combination with 5-fluorouracil (5FU), cyclophosphamide (CYT) or mitomycin C (MMC). The preliminary results indicated that combination treatment seemed to possess better antitumor activity than chemotherapy alone. The treatment with CHC alone however had neither an obvious antitumor effect in tumor bearing mice nor toxicity in normal mice. These results show that CHC may stimulate organs of the immune system such as the spleen to be im-munomodulators and enhance the antitumor activity of some chemotherapeutic agents.

Adhesion and immunomodulatory effects of Bifidobacterium lactis HN019 on intestinal epithelial cells INT-407

AIM:To elucidate the adherence and immunomodulatory properties of a probiotic strain Bifidobacterium lactis(B.lactis) HN019.METHODS:Adhesion assays of B.lactis HN019 and Salmonella typhimurium(S.typhimurium) ATCC 14028 to INT-407 cells were carried out by detecting copies of species-specific genes with real-time polymerase chain reaction.Morphological study was further conducted by transmission electron microscopy.Interleukin-1β(IL-1β),interleukin-8,and tumor necrosis factor-α(TNF-α) gene expression were assessed while enzyme linked immunosorbent assay was used to detect IL-8 protein secretion.RESULTS:The attachment of S.typhimurium ATCC 14028 to INT407 intestinal epithelial cells was inhibited significantly by B.lactis HN019.B.lactis HN019 could be internalized into the INT-407 cells and attenuated IL-8 mRNA level at both baseline and S.typhimuriuminduced pro-inflammatory responses.IL-8 secretion was reduced while IL-1β and TNF-α mRNA expression level remained unchanged at baseline after treated with B.lactis HN019.CONCLUSION:B.lactis HN019 does not up-regulate the intestinal epithelium expressed pro-inflammatory cytokine,it showed the potential to protect enterocytes from an acute inflammatory response induced by enteropathogen.

Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration

Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.

Antiviral,immunomodulatory,and anticoagulant effects of quercetin and its derivatives:Potential role in prevention and management of COVID-19

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has caused a devastating health crisis worldwide.In this review,we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic.The following evidence supports our argument.First,nuclear factor erythroid-derived 2-like 2(NRF2)agonists abrogate replication of SARS-CoV-2 in lung cells,and quercetin is a potent NRF2 agonist.Second,quercetin exerts antiviral activity against several zoonotic coronaviruses,including SARS-CoV-2,mainly by inhibiting the entry of virions into host cells.Third,inflammatory pathways activated by nuclear factor kappa B,inflammasome,and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19,and quercetin inhibits these pro-inflammatory signals.Fourth,patients with COVID-19 develop thrombosis,and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase.This review provides a strong rationale for testing quercetin for the management of COVID-19.

Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms

BACKGROUND Mesenchymal stem cells(MSCs)are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties.Although human bone marrow-derived MSCs(BM-MSCs)were the most widely used MSCs in cell therapy until recently,MSCs derived from human umbilical cords(UC-MSCs)have gained popularity as cell therapy material for their ethical and noninvasive collection.AIM To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs.METHODS To analyze soluble factors expressed by MSCs,such as indolamine 2,3-dioxygenase,cyclooxygenase-2,prostaglandin E2 and interleukin(IL)-6,inflammatory environments in vitro were reconstituted with combinations of interferon-gamma(IFN-γ),tumor necrosis factor alpha and IL-1βor with IFN-γalone.Activated T cells were cocultured with MSCs treated with indomethacin and/or anti-IL-10.To assess the ability of MSCs to inhibit T helper 17 cells and induce regulatory T cells,induced T helper 17 cells were cocultured with MSCs treated with indomethacin or anti-IL-10.Xenogeneic graft-versus-host disease was induced in NOG mice(NOD/Shi-scid/IL-2Rγnull)and UC-MSCs or BM-MSCs were treated as cell therapies.RESULTS Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation abilities.BM-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ,tumor necrosis factor alpha-αand IL-1βor IFN-γalone.UC-MSCs expressed more prostaglandin E2,IL-6,programmed death-ligand 1 and 2 in the in vitro inflammatory environment.Cyclooxygenase-2 and IL-10 were key factors in the immunomodulatory mechanisms of both MSCs.In addition,UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than BM-MSCs.UC-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host disease.CONCLUSION UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms involved.These findings suggest that UC-MSCs have distinct immunoregulatory functions and may substitute BM-MBSCs in the field of cell therapy.

Umbilical cord-derived mesenchymal stem cells retain immunomodulatory and anti-oxidative activities after neural induction

The immunomodulatory and anti-oxidative activities of differentiated mesenchymal stem cells contribute to their therapeutic efficacy in cell-replacement therapy. Mesenchymal stem cells were isolated from human umbilical cord and induced to differentiate with basic fibroblast growth factor, nerve growth factor, epidermal growth factor, brain-derived neurotrophic factor and forskolin. The mesenchymal stem cells became rounded with long processes and expressed the neural markers, Tujl, neurofilament 200, microtubule-associated protein-2 and neuron-specific enolase. Nestin expression was significantly reduced after neural induction. The expression of immunoregulatory and anti-oxidative genes was largely unchanged prior to and after neural induction in mesenchymal stem cells. There was no significant difference in the effects of control and induced mesenchymal stem cells on lymphocyte proliferation in co-culture experiments. However, the expression of human leukocyte antigen-G decreased significantly in induced neuron-like cells. These results suggest that growth factor-based methods enable the differentiation of mesenchymal stem cell toward immature neuronal-like cells, which retain their immunomodulatory and anti-oxidative activities.

The potential role of grape (Vitis vinifera L.) in prevention of threatened abortion via immunomodulatory and anti-inflammatory abilities: a hypothesis

Threatened abortion is a common problem in early pregnancy. This early vaginal bleeding happens in about 25% of pregnant women. The medications including progesterone, uterine muscle relaxant or human chorionic gonadotropin have essential effects in developing pregnancy, but the clinical data are insufficient to prescribe them. In recent decades, medicinal herbs can help us to present new treatments. Grape (Vitis vinifera L.) can protect the fetus from the perspective of Persian medicine. So, we hypothesize about the salutary effects of grape in miscarriage prevention. We found five standard expected mechanisms of grape to prevent threatened abortion: immunomodulatory and anti-inflammatory, anti-oxidant, anti-contraction, hormonal and anti-stress activities. Grape reduces nitric oxide, prostaglandin E2, expression of nuclear factor κB and other pro-inflammatory cytokines like IL (Interleukin)-1β, IL-6, IL-8, and tumor necrosis factor-α. It also elevates anti-inflammatory mediators and expression of peroxisome proliferator-activated receptor-γ. Grape polyphenols have a crucial role in fetus protection with high antioxidant power and other functions such as prevention of stress-triggered abortion with proanthocyanidins, or hormonal effects and inhibition of uterine contractions with resveratrol. So according to these studies, grape probably has effects on the immune and endocrine factors involved in threatened miscarriage.

DISEASE RESISTANCE AND HUMORAL IMMUNOMODULATORY EFFECTS OF VITAMIN C ON GROUPER, EPINEPHELUS AWOARA

The disease resistance and humoral immunomodulatory effects of vitamin C administered orally to grouper, Epinephelus awoara maintained on a frozen fish diet supplemented with vitamin C at 500, 1000, 1500 and 2000 mg/kg were investigated. After 20 weeks, the growth rates of the groups with high level of vitamin C apparently increased. The untreated fish had symptoms of vitamin C deficiency. The endogenous liver tissue vitamin C levels were found to reflect well the dietary treatments. After intraperitoneal injection or bath challenge with a virulent strain of Vibrio vulnificus , fish fed with high level vitamin C showed significantly higher survival rate compared with the normal control group. Vaccination with formalin inactivated V. vulnificus significantly enhanced the specific antibody production in fish treated with vitamin C, and completely protected from strong bacterial challenge the groups fed on fish with vitamin C 1500 and 2000 mg/kg diet.