Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

Expression and Clinical Significance of Various Cytokines in Otitis Media

The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of cytokine transduction pathways. More and more studies have shown that relevant cell proliferation and inflammation progression pathways play a role in the development of otitis media, such as the Jun amino-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway, the NF-κB signaling pathway, and the PI3K/AKT/PTEN pathway, which are involved in the proliferation of the middle ear mucosa during otitis media, which affects the mucosal cilia, motor function, Eustachian tube function, and the mucosal ciliary function. These studies provide new ideas for the treatment of otitis media and further explore the feasibility of immunotherapy in the future treatment of otitis media. In this paper, we present a review of the latest research progress on the expression of various cytokines in otitis media.

Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines

BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.

Serum level changes of inflammatory cytokines in patients with moderate to severe acne vulgaris treated with dual-wavelength laser

Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used to treat AV;however,the serum level changes of inflammatory cytokines after laser therapy have not been elucidated.We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595-and 1064-nm dualwavelength laser.Methods:In total,18 patients(9 male and 9 female)between 16 and 35 years of age with moderate to severe AV were evaluated in the study.Disease severity was classified according to the Pillsbury grading system of acne.Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment.A 3 mL blood sample was drawn from every subject each time,and serum levels of inflammatory cytokines such as interleukin(IL)-6,IL-8,and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment.Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation.Results:Inflammation was significantly reduced on both the treated and untreated sides,and symptoms of AV lesions were alleviated.All patients showed a significant increase in serum IL-22 levels after the first laser therapy,with no significant difference in serum IL-6 and IL-8 levels.After the second laser therapy,serum IL-6,IL-8,and IL-22 levels were significantly decreased.No significant side effects such as bruising,edema,hyperpigmentation,hypopigmentation,or scarring were reported.Conclusion:Half-face treatment with 595-and 1064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission,which was associated with a gradual decrease in IL-6,IL-8,and IL-22 levels after half-face topical treatment.This suggests that reducing inflammatory cytokine levels in the serum can relieve inflammation in non-therapeutic sites.This laser treatment is effective,economical,and painless.

Cytokines,synaptic plasticity and network dynamics:a matter of balance

The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized.However,the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled.To control cognitive function and behavior,the two systems are engaged in a subtle interacting act.In this scenario,a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging.Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes.In this dynamic equilibrium,synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro-and anti-inflammatory molecules in the central nervous system microenvironment.

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.

Perspective on inflammatory cytokines in open spinal dysraphism

Myelomeningocele(MMC)is a severe form of spinal dysraphism.Due to the failure of neural tube closure during early embryonic development,the affected part of the spinal cord is left open like a book at the back of the affected child.This malformed part of the spinal cord is not covered by its protective mesodermal and ectodermal derived layers.Consequently,the exposed neural tissue(i.e.,the neural placode)is prone to injuryduring further intra-uterine development.

Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing

Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.

Effect of acupuncture on acupoint "Yingxiang-Hegu" on Th1, Th2 cytokines and T-bet/GATA-3 of allergic rhinitis rats

Objective:To explore the effect of"Yingxiang-Hegu"on Th1,Th2-related cytokines and[2]transcription factors T-bet and GATA-3 in rats with allergic rhinitis.Methods:Rats were randomly divided into three groups:blank group,model group and acupoint group.The rat model of ovalbumin(OVA)AR was established,and the general condition of the rats was observed and scored.Acupuncture intervention was performed on the acupoint group on the second day after successful modeling,once per day for 20 min for 10 d.After intervention,the general behavior,behavioral score and histomorphological changes of nasal mucosa were observed.Eosinophils(EOS)were counted under microscope after nasal lavage smear staining,and the contents of total IgE,IFN-γ,IL-12,IL-4 and IL-5 in serum were detected by ELISA.Westernblot and IHC were used to detect the protein level and positive protein expression of specific transcription factors T-bet and GATA-3 in rat nasal mucosa.Results:After the establishment of the model,except for the blank group,the behavioral observation scores of rats in the model group and acupoint group were more than 5 points,indicating that the model was successful.After acupuncture intervention on acupoint"Yingxiang-Hegu",the behavioral score of rats in the acupoint group and western medicine group was significantly lower than that in the model group(P<0.05).Microscopic examination showed that the structure of nasal mucosa in the model group was obviously damaged,cilia were arranged discontinuously,uneven,local congestion and swelling,a large number of epithelial cells exfoliated and necrotic,goblet cell proliferation,obvious inflammatory cell infiltration.The pathological degree of nasal mucosa in the pair point group was significantly less than that in the model group.Compared with the model group,the levels of IFN-γ,IL-2 and IL-12 in serum were significantly increased,while IgE,IL-4,IL-5 and IL-6 were significantly decreased,GATA-3 protein and positive expression in nasal mucosa were significantly decreased and T-bet was significantly increased after acupuncture.Conclusion:Acupuncture at"Yingxiang-Hegu"can effectively improve the nasal sensitive symptoms and control nasal inflammation in AR rats.The mechanism may be that acupuncture at Yingxiang-Hegu can up-regulate the expression of T-bet,decrease the level of GATA-3,promote the production of Th1 cytokines and inhibit the synthesis and secretion of Th2 cells,thus restoring the immune balance of Th1 and Th2.

Pro-inflammatory cytokines levels in tears and dry eye disease in Parkinson’s disease

Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.

Effects of Kangfuxin Solution (康复新液) Combined with Low-level Laser on Cytokines and Immune Function in Patients with Radiation-induced Oral Mucositis

Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.

Dual-directional regulation of spinal cord injury and the gut microbiota

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

The anti-inflammatory effects of exercise on autoimmune diseases:A 20-year systematic review

Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne factors.Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and neurogenesis.Methods:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise.For in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)saline.Cognitive function,amyloid plaque pathology,and neurogenesis were assessed.The plasma used for the treatment was analyzed for 23 cytokines.Results:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(p<0.001)in amyloid-β-treated cells.In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated rats.Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma.Conclusion:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain.This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

Coumarin and eugenol ameliorate LPS-induced inflammation in RAW 264.7 cells via modulating the NLRP3 inflammasome pathway

Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

Anemarsaponin B mitigates acute pancreatitis damage in mice through apoptosis reduction and MAPK pathway modulation

Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.