Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains unexplored.To investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed patients.Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further analyses.Clinical metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis.Subsequent western blot analyses validated key findings.Finally,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression.Periodontitis progression was identified as occurring at a faster rate than traditionally thought.GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles.In addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of periodontitis.Moreover,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis.Additionally,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis.Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal disease.These findings may lead to novel diagnostic and therapeutic strategies.

Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

Proximate analyses,in vitro antioxidant activity and GC-MS analyses of fermented Pentaclethra macrophylla seeds

The present study assessed the proximate composition,in vitro antioxidant activity and GC-MS analyses of fermented Pentaclethra macrophylla seeds extract(FPMSE).The in vitro antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazl(DPPH)while Gas Chromatography-Mass Spectrophotometry(GC-MS)technique was used to identify the volatile compounds in FPMSE.FPMSE revealed a dose dependent percentage inhibition of the extract on DPPH assay.Proximate composition of FPMSE constitutes respectively;ash(0.33±0.12%),protein(2.19±0.08%),fats and oil(80.60±0.00%),carbohydrate(16.88±0.00%)while moisture and fibre were not detected.However,the pulverised sample constitute respectively;ash(1.27±0.58%),protein(10.51±0.60%),moisture(8.27±0.12%),fats and oil(32.33±0.12%),fibre(7.27±0.12%)and carbohydrate(40.35±0.00%).GC-MS analyses revealed fourteen(14)fatty acids including Octadecanoic acid(1.95%),Benzyloxymethylimine(43.89%),2-Allylpent-4-enoic acid benzyl ester(26.25%),Hexadecanoic acid,methyl ester(1.09%),Oleic Acid(0.25%),9,12-Octadecadienoic acid,methyl ester(Omega-6-fatty acid)(1.52%).The bioactive compounds identified in FPMSE could contribute to the pharmacological properties of P.macrophylla seeds and hence,could be of considerable interest for the development of new drugs.

The biomedical significance of the phytochemical, proximate and mineral compositions of the leaf, stem bark and root of Jatropha curcas

Objective: To analyse the phytochemical contents of leaf, stem bark and root of Jatropha curcas(J. curcas) in four solvent extracts and their proximate and mineral compositions. Methods: Standard analytical procedures were used for the determination of phytochemicals, proximate and mineral compositions of the leaf, stem bark and root extracts of J. curcas. Results: Results of the analysis showed the presence of polyphenols, flavonoids, alkaloids, cardiac glycosides, coumarins, saponins, terpenoids, steroids, triterpenoid saponins, carotenoids, phlobatannins and tannins in the leaf, stem bark and root of all the solvent extracts. Flavonoids were present in the highest amount in the ethyl acetate extracts of the leaf(7.35% ± 0.02%), stem bark(4.12% ± 0.01%) and root(3.35% ± 0.02%) followed by polyphenols in the methanol extracts of leaf(4.62% ± 0.02%), stem bark(2.77% ± 0.05%) and root(2.49% ± 0.02%). Poly-acetylated compounds were absent in all the solvent extracts of the leaf, stem bark and root. However, some anti-nutritional agents such as oxalates, phytates and cyanates were present in all the solvent extracts of the leaf, stem bark and root except the ethyl acetate. Phytates were high in the aqueous solvent of the leaf(6.12% ± 0.00%) but low in the stem bark(1.00% ± 0.05%) and root(0.89% ± 0.03%). Proximate composition showed appreciable amounts of total carbohydrate(36.33% ± 0.72%), crude protein(26.00% ± 0.47%) and reducing sugars(5.87% ± 0.14%) in the leaf, while crude fat was more in the stem bark(16.70% ± 0.30%). There was corresponding substantial energy in the leaf [(1 514.77 ± 20.87) kJ /100 g] and stem bark [(907.00 ± 8.52) kJ /100 g]. Moisture and ash contents of the leaf, stem bark and root were within acceptable limits for the use in drugs formulation. The mineral composition showed substantial amounts of important elements such as Fe, Ca, Na, Mg and Zn. Others were P, K and Se. Conclusions: The outcome of this study suggests that the leaf, stem bark and root of J. curcas have very good medicinal potentials, meet the standard requirements for drug formulation and serve as good sources of energy and nutrients except for the presence of some anti-nutritional elements predominant in the leaf.

Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.

From precise diagnosis to effective treatment:a case report of atypical Cogan's syndrome

Dear Editor,We present the reported case of a 37-year-old male atypical Cogan’s syndrome(CS)patient who was precisely diagnosed and clinically cured under our systematic therapeutic regime.CS is a rare autoimmune disorder involving the eye,characterised by interstitial keratitis(IK)and the auditory-vestibulo system with vestibular dysfunction.

The medicinal chemistry of Urtica dioica L.:from preliminary evidence to clinical studies supporting its neuroprotective activity

Urtica dioica is a perennial herb from the family of Urticaceae that is commonly known as stinging nettle.This plant is widespread in Europe,Africa,America,and a part of Asia,as it adapts to different environments and climatic condi-tions.The leaves,stalk,and bark of U.dioica found applications in the field of nutrition,cosmetics,textile,pest control and pharmacology.In this connection,bioactive chemical constituents such as flavonoids,phenolic acids,amino acids,carotenoids,and fatty acids have been isolated from the plant.With this review,we aim at providing an updated and comprehensive overview of the contributions in literature reporting computational,in vitro,pre-clinical and clini-cal data supporting the therapeutic applications of U.dioica.Experimental evidence shows that U.dioica constituents and extracts can provide neuroprotective effects by acting through a combination of different molecular mecha-nisms,that are discussed in the review.These findings could lay the basis for the identification and design of more effective tools against neurodegenerative diseases.

Synergistic Mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera Aqueous Extract: Its Liver and Kidney Benefits in Male Albino Rat Model

Background: The synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract is a common drink in Port Harcourt, Nigeria. It is assumed to have various health benefits. However, the synergistic mixture of the content has not been studied scientifically, hence the need to evaluate its effect on the liver and kidney being part of the body’s metabolic organs. Aim: This study evaluated the synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract in male albino rats. Methods: Acute toxicity LD50 of STCD was carried out, afterwards, fifteen male albino rats were grouped into three groups with 5 rats in each group;Control, 200 mg/kg, 400 mg/kg STCD. The rats were administered STCD orally 24 hourly, for 21 days, with feed and water ad libitum. At the end of the experiment, blood samples were collected for biochemical analysis of the liver and kidney biomarkers, while the liver and kidney tissues were harvested for histopathological examination using standard laboratory methods. Descriptive statistics were computed and expressed as Mean ± SD. One-way ANOVA and Turkeys test was performed. P value ≤0.05 was considered statistically significant. Results: Acute toxicity LD50 of STCD was observed to be ≥2404.2 mg/kg body weight. An increase in the percentage body weight difference of 8.39% and 2.86% was observed for 200 and 400 mg/kg STCD groups. Also, the liver weight was observed to increase in 400 mg/kg (3.92 ± 1.42) in comparison to the control group (3.48 ± 1.61), a decrease in the kidney weight was observed in all groups administered STCD in comparison to the control group. Administration of STCD at both 200 and 400 mg/kg revealed a decrease in the concentration of the hepatic biomarkers AST, ALT, ALP, TP, Albumin, Total and conjugated bilirubin. The kidney biomarker Urea was observed to decrease in concentration for 200 mg/kg STCD (4.60 ± 1.83) and 400 mg/kg STCD (4.76 ± 0.74) when compared to the control group (6.32 ± 2.74). A decrease in Creatinine was observed in 200 mg/kg (91.80 ± 34.69) and 400 mg/kg (98.60 ± 15.53) in comparison to the control group (117.60 ± 42.88). The histological examination of the liver of rats administered STCD revealed structural normal central vein, hepatocytes and portal tract. The kidney examination revealed normal glomeruli and normal tubule. Conclusion: The findings of this study opine that STCD improved the health of both the liver and kidney as evidenced via the biomarkers and histological examinations of the liver and kidney. This study therefore recommends the intake of STCD at moderate doses for improved liver and kidney function due to its bioactive compounds and nutritional content.

Systematics of the avian family Alaudidae using multilocus and genomic data

The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.

Lipoprotein (a) Cut-Off in Chronic Kidney Disease Patients with a History of Cardiovascular Disease in Center Hospital University Souro SANOU, Burkina Faso

Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiovascular disease (CVD). This was a cross-sectional study. Variables including age, sex, history of CVD, body mass index and CKD stage, were collected during CKD patient’s first admission in the nephrology dialysis department. Blood samples were collected for quantitative determination of Lp(a) by immunoturbidimetric method. They were divided into two groups: CKD patients without history of CVD and CKD patients with history of CVD. Fisher’s exact test was used to assess associations with a significance level of 0.05%. Area under the curve (AUC) and new cut-off value for Lp(a) were identified by drawing Receiver Operating Characteristic (ROC) curve. A total of seventy CKD patients with median age of 43 years [minimum-maximum = 15 - 78 years] were included. Patients with history of CVD were 65.71% (46/70). New Lp(a) cut-off point in CKD patients with history of CVD was 66.50 nmol/L [sensitivity, 87.00%;specificity, 58.30%;AUC = 0.727;p = 0.000]. ROC curve demonstrated good performance of Lp(a) to screen CKD patients with history of CVD. Further research is needed to determine an LPA gene polymorphism’s contribution to increasing risk for CVD at each kidney disease stage.

Assessment of thiol/disulfide homeostasis for prognostic follow-up of cholangiocarcinoma patients

Background:Cholangiocarcinoma(CCA)is a cancer type that builds in the bile ducts that carry digestive fluid,bile.These ducts connect the liver to the gallbladder and the small intestine.The disease is often diagnosed at an advanced stage,resulting in a low 5-year survival rate.This study aims to evaluate the concentrations of serum thiol/disulfide in CCA patients and healthy volunteers and investigate the association between oxidative activity and clinical and pathological characteristics in CCA patients.By examining the relationship between reduced thiol/disulfide measures and tumorigenesis of the disease,we can potentially identify an unfavourable prognosis in CCA patients.Methods:To assess the status of thiol/disulfide in the blood of Cholangiocarcinoma patients using a novel automated homeostasis assay,we recruited 55 individuals for this study(CCA patients,n=27;healthy volunteers,n=28).We measured the levels of serum total thiol(TT)(–SH+–S-S–),native thiol(NT)(–SH),and disulfide(DD)(–S-S–)in both the CCA group and the control group.Additionally,we calculated the ratio of thiol/disulfide(–SH/–S-S–).Results:We explored the relationship between oxidative activity and clinical and pathological characteristics in CCA patients.The study found no significant differences in age and sex between CCA patients and controls.NT and TT levels were higher in the control group compared to the CCA group.However,the disulfide level did not significantly differ between the two groups.Pearson's correlation matrix analysis revealed positive correlations between TT and NT levels and negative correlations between NT/TT%,DD level,and DD/TT%.Conclusion:Our findings suggest a statistical difference in serum thiol/disulfide parameters.As a marker of total oxidant status,thiol and disulfide levels have decreased in patients with CCA.However,no correlation was found between the tumour markers CEA and CA19-9 and thiol levels.A decrease in blood thiol and disulfide concentrations or the ratio of thiol to disulfide may indicate an increase in oxidative stress and decreased antioxidant capacity.As an indication of the prognosis of cholangiocarcinoma disease in the early period,it may be used to determine the effectiveness of medical interventions.The NT/TT%,disulfide/native thiol percentage,and DD/TT%ratios did not significantly change between the groups.Therefore,measuring serum thiol levels could be a helpful marker for assessing prognosis in the early stages of CCA.Nevertheless,further studies must validate these results and investigate the underlying mechanisms.

Cellular preconditioning and mesenchymal stem cell ferroptosis

In this editorial,we comment on the article published in the recent issue of the World Journal of Stem Cells.They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary hypertension.Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured tissue.They also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell survival.Ferroptosis,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to cancer.The lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular structures.Understanding these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related diseases.This editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis pathway.Ferroptosis presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention.Further research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery

BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coinfection with Malaria in Selected States in Nigeria

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium species are the causative agents of coronavirus disease 2019 (COVID-19) and malaria respectively with similar clinical presentations. The objective of this study is to determine the burden of co-infection of SARS-CoV-2 and malaria in the general population. Five (5 mLs) of blood samples were collected for SARS-CoV-2 and malaria parasite test. The malaria test was performed using a commercially available one-step malaria antigen Plasmodium falciparum histidine-rich protein 2 (Pf HRP-II) rapid test kit. The results of the study showed that the participants that were coinfected with SARS-CoV-2 IgG and malaria were 13 (2.5%) in Lagos, 1114 (39.1%) in Delta and 49 (2.3%) in Sokoto States. The prevalence of coinfection of SARS-CoV-2 and malaria in urban areas in Lagos, Delta and Sokoto States were 7 (2.2%), 1373 (48.1%), and 5 (0.2%) respectively. In rural areas, the prevalence of coinfection of SARS-CoV-2 and malaria in Lagos, Delta and Sokoto States were 6 (0.3%), 365 (12.8%), and 44 (2.1%) respectively in this study. This suggests that participants in the urban areas were more prone to co-infections than the rural areas in Lagos and Delta states, while it was otherwise in Sokoto State. In conclusion, the co-infection of SARS-CoV-2 and malaria was very high in Delta State compared to the other States. It is important for clinics to screen for both diseases when patients present with symptoms of malaria. This is because the infections have similar symptoms and the public is quick to assume malaria infection without diagnosing for COVID-19 and vice versa.

Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury

Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties.We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury.In this study,rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1,7,and 14 days after cavernous nerve injury.Serum superoxide dismutase and glutathione peroxidase activities significantly increased at 1 and 2 weeks post-injury.Serum malondialdehyde levels decreased at 2 and 4 weeks.At 12 weeks,peak intracavernous pressure,the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-positive nerve fibers,levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury.These findings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery.This neuroregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury.

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases(IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis.These idiopathic diseases have environmental, genetic,immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type(Th) 1 and Th2 immune responses,other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin,microRNAs, and serum proinflammatory cytokines.An efficient strategy for IBD therapy is represented by the combination of IL-17 A and IL-17 F in acute IL-17 A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17 F knockout, DSS-induced colitis have been observed.Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused reviewin order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.

Relationship between acrosin activity of human spermatozoa and oxidative stress

Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

Phytochemical analysis and anticancer capacity of Shemamruthaa,a herbal formulation against DMBA-induced mammary carcinoma in rats

Objective:To investigate the bioactive-constituents of Shemamruthaa(SM),a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation(LPO),antioxidant status,citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene(DMBA)induced mammary carcinoma in rat model.Methods:Adult Female Sprague-Dawley rats were used for the study and were divided into four groups.CroupⅠserved as control and CroupⅡrats were induced mammary carcinoma by administration of DMBA(25 mg/kg b.w.)orally.The normal and cancer-induced rats(GroupⅢ)were treated with SM(400 mg/kg b.w./day)orally by gastric incubation for 14days.CroupⅣrats served as SM-treated control animals.Results:Cancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants,citric acid cycle enzymes,electron transport chain enzymes and cytochrome contents in the mammary tissue.Treatment with SM brought back the aforementioned biochemical parameters to near normal.Conclusions:From the results,it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO,prevention of membrane damage and restoring membrane integrity.