Application of EdU-Based DNA Synthesis Assay to Measure Hepatocyte Proliferation In Situ During Liver Regeneration.

Monitoring hepatocyte proliferation in situ following partial hepatectomy is widely used to characterize cytokines, growth factors and signaling molecules and pathways as well as the regulatory mechanisms involved in liver regeneration. Periodic measurement of the liver/body mass ratio estimates the rate of liver regeneration, which is often supplemented by evaluating the proportion of proliferating hepatocytes using a synthetic nucleoside analog such as 5-bromo-2'-deoxyuridine (BrdU) or the nuclear accumulation of proliferating cell nuclear antigen (PCNA) in proliferating cells. The introduction of the thymidine analog 5-ethynyl-2'deoxyuridine (EdU) and its detection by "click chemistry" using fluorescently labeled reagents has simplified the evaluation of live cell proliferation as it eliminates certain limitations of antibody-mediated detection of BrdU. Here, we describe the EdU-based measurement of hepatocyte proliferation during liver regeneration and correlate the results with that of Ki67 and PCNA-based assays.

Cardioprotective effect of silicon-built restraint device (ASD), for left ventricular remodeling in rat heart failure model.

This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat's heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD's functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).

Therapeutic interventions to urologic chronic pelvic pain syndrome and UPOINT system for clinical phenotyping: How far are we?

The assessment and management of urologic chronic pelvic pain syndrome (UCPPS), is controversial. It is classified by voiding symptoms, pelvic pain, and bladder pain, which is weekly treated, weekly understood, and bothersome. In the aspect of clinical efforts and research to help people with this syndrome have been hampered by the deficiency of a widely reliable, accepted, and a valuable tool to evaluate the patient symptoms and quality of life (QoL) impact. However, the etiology comes into sight is multifactorial, and available treatment options have been imprecise considerably in present years. We compiled the published literature on the assessment of the syndrome, a tentative role of pharmacological and non-pharmacological (conservative, alternative, and invasive therapy) interventions in eradicating the disease as well as improving symptoms. The previously published literature on animal models has established the association of immune systems in the etiology, pathogenesis, and progression of the disease. The UPOINT system for clinical phenotyping of UCPPS patients has six predefined domains that direct multimodal therapy, which would lead to significant symptom improvement in the medical field. The narrative review aims to scrutinize the fluctuating scientist's views on the evaluation of patient and multimodal treatment of the UPOINT system.

SILAC proteomics implicates SOCS1 in modulating cellular macromolecular complexes and the ubiquitin conjugating enzyme UBE2D involved in MET receptor tyrosine kinase downregulation.

Suppressor of Cytokine Signaling 1 (SOCS1) functions as a tumor suppressor in hepatocellular carcinoma and many other types of cancers. SOCS1 mediates its functions by inhibiting tyrosine kinases, promoting ubiquitination and proteasomal degradation of signal transducing proteins, and by modulating transcription factors. Here, we studied the impact of SOCS1 on the hepatocyte proteome using Stable Isotopic Labelling of Amino acids in Cell culture (SILAC)-based mass spectrometry on the Hepa1-6 murine HCC cell line stably expressing wildtype SOCS1 or a mutant SOCS1 with impaired SH2 domain. As SOCS1 regulates the hepatocyte growth factor (HGF) receptor, the MET receptor tyrosine kinase (RTK), the SILAC-labelled cells were stimulated or not with HGF. Following mass spectrometry analysis, differentially modulated proteins were identified, quantified and analyzed for pathway enrichment. Of the 3440 proteins identified in Hepa-SOCS1 cells at steady state, 181 proteins were significantly modulated compared to control cells. The SH2 domain mutation and HGF increased the number of differentially modulated proteins. Protein interaction network analysis revealed enrichment of SOCS1-modulated proteins within multiprotein complexes such as ubiquitin conjugating enzymes, proteasome, mRNA spliceosome, mRNA exosome and mitochondrial ribosome. Notably, the expression of UBE2D ubiquitin conjugating enzyme, which is implicated in the control of growth factor receptor tyrosine kinase signaling, was found to be regulated by SOCS1. These findings suggest that SOCS1, induced by cytokines, growth factors and diverse other stimuli, has the potential to dynamically modulate of large macromolecular regulatory complexes to help maintain cellular homeostasis.

A glimpse into the efficacy of alternative therapies in the management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease that can cause uncomfortable lower urinary tract symptoms. The occurrence of symptomatic BPH develops after the age of 40 years and increases gradually with age to reach more than 50% at the age of 60 years and severely disturbs the quality of life of the patients. Alpha-blockers and 5­alpha reductase inhibitors are first-line agents used for the treatment of BPH. Due to the adverse effects of these conventional therapies, many patients turn to phytotherapy and other alternative therapies. This review covers alternative therapies, i.e., phytotherapy (cernilton, eviprostat, quercetin, saw palmetto and pumpkin seed) and physical therapy (acupuncture, aquablation, pulsed electromagnetic field, prostate urethral lift, radial extracorporeal shock wave therapy, thermobalancing therapy, and transurethral needle ablation) commonly used in the management of BPH.

ADE and hyperinflammation in SARS-CoV2 infection- comparison with dengue hemorrhagic fever and feline infectious peritonitis.

The COVID-19 pandemic has rapidly spread around the world with significant morbidity and mortality in a subset of patients including the elderly. The poorer outcomes are associated with 'cytokine storm-like' immune responses, otherwise referred to as 'hyperinflammation'. While most of the infected individuals show minimal or no symptoms and recover spontaneously, a small proportion of the patients exhibit severe symptoms characterized by extreme dyspnea and low tissue oxygen levels, with extensive damage to the lungs referred to as acute respiratory distress symptom (ARDS). The consensus is that the hyperinflammatory response of the host is akin to the cytokine storm observed during sepsis and is the major cause of death. Uncertainties remain on the factors that lead to hyperinflammatory response in some but not all individuals. Hyperinflammation is a common feature in different viral infections such as dengue where existing low-titer antibodies to the virus enhances the infection in immune cells through a process called antibody-dependent enhancement or ADE. ADE has been reported following vaccination or secondary infections with other corona, Ebola and dengue virus. Detailed analysis has shown that antibodies to any viral epitope can induce ADE when present in sub-optimal titers or is of low affinity. In this review we will discuss ADE in the context of dengue and coronavirus infections including Covid-19.

Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma.

BACKGROUND: SOCS1 and SOCS3 genes are considered tumor suppressors in hepatocellular carcinoma (HCC) due to frequent epigenetic repression. Consistent with this notion, mice lacking SOCS1 or SOCS3 show increased susceptibility to diethylnitrosamine (DEN)-induced HCC. As SOCS1 and SOCS3 are important regulators of cytokine and growth factor signaling, their loss could activate oncogenic signaling pathways. Therefore, we examined the correlation between SOCS1/SOCS3 and key oncogenic signaling pathway genes as well as their prognostic significance in HCC. METHODS: The Cancer Genome Atlas dataset on HCC comprising clinical and transcriptomic data was retrieved from the cBioportal platform. The correlation between the expression of SOCS1 or SOCS3 and oncogenic pathway genes was evaluated using the GraphPad PRISM software. The inversely correlated genes were assessed for their impact on patient survival using the UALCAN platform and their expression quantified in the regenerating livers and DEN-induced HCC tissues of mice lacking Socs1 or Socs3. Finally, the Cox proportional hazards model was used to evaluate the predictive potential of SOCS1 and SOCS3 when combined with the genes of select oncogenic signaling pathways. RESULTS: SOCS1 expression was comparable between HCC and adjacent normal tissues, yet higher SOCS1 expression predicted favorable prognosis. In contrast, SOCS3 expression was significantly low in HCC, yet it lacked predictive potential. The correlation between SOCS1 or SOCS3 expression and key genes of the cell cycle, receptor tyrosine kinase, growth factor and MAPK signaling pathways were mostly positive than negative. Among the negatively correlated genes, only a few showed elevated expression in HCC and predicted survival. Many PI3K pathway genes showed mutual exclusivity with SOCS1 and/or SOCS3 and displayed independent predictive ability. Among genes that negatively correlated with SOCS1 and/or SOCS3, only CDK2 and AURKA showed corresponding modulations in the regenerating livers and DEN-induced tumors of hepatocyte-specific Socs1 or Socs3 deficient mice and predicted patient survival. The Cox proportional hazards model identified the combinations of SOCS1 or SOCS3 with CXCL8 and DAB2 as highly predictive. CONCLUSIONS: SOCS1 expression in HCC has an independent prognostic value whereas SOCS3 expression does not. The predictive potential of SOCS1 expression is increased when combined with other oncogenic signaling pathway genes.

Factors Influencing the Delivery Efficiency of Cancer Nanomedicines.

The superiority of nanomedicine over conventional medicines in the treatment of cancer has gained immediate recognition worldwide. As traditional cancer therapies are nonspecific and detrimental to healthy cells, the ability of nanomedicine to release drugs to target tumor cells specifically instead of healthy cells has brought new hope to cancer patients. This review focuses on the effects of various factors of nanoparticles such as transport, concentration in cells, tumor microenvironment, interaction with protein, penetration, uptake by tumor cells, cancer cell mutations, and intracellular trafficking of the nanoparticle. Besides the history of nanomedicine, future perspectives of nanomedicines are also explored in this text.

Antibody-Drug Conjugates: A Comprehensive Review.

Antibody-drug conjugates (ADC) are one of the fastest growing anticancer drugs. This approach comprises a mAb conjugated to the cytotoxic payload via a chemical linker that directed toward a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. ADCs are complex molecules that require careful attention to various components. Selection of an appropriate target, an mAb, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC, and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design. Moreover, this review also shed light on the current status of ADCs that have gained regulatory approval from the FDA including a description of biology and chemistry, metabolic profiles, adverse events, drug interactions, and the future perspective on combination strategies with other agents, including immunotherapy.

Morphological reseach on expression of inflammatory mediators in murine models of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by T2 antigen.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common clinical syndrome with unknown aetiology. In this study, we used the T2 peptide in C57BL/6 (B6) mice and Sprague Dawley (SD) rats model during different stages. We sought to understand the role of CD4+ T cells and macrophages in CP/CPPS. A total of 16 B6 mice and 18 SD rats were divided into five groups: B6-naïve (n = 6), B6 model (n = 10), SD-naïve (n = 6), SD-45-day model (n = 6) and SD-56-day model (n = 6). The B6 model group was subcutaneously injected with 0.2 ml of (225µg/ml) T2 peptide on 0 and 14th day and was finally sacrificed on 28th day. The SD-45- and SD-56-day model groups were subcutaneously injected with 1ml of (50 µg/ml) T2 peptide on 0 and 14th day and were finally sacrificed on 45th and 56th day respectively. An equivalent volume of normal saline (NS) solution was injected to the naïve groups and analysed the pain and voiding behaviour. We have calculated the prostate index, H&E staining and immunofluorescence of CD4+ T cells and macrophages (CD68) in each group. T2 peptide immunization in B6 mice and SD rats caused severe prostatitis and cell infiltration, mainly composed of CD4+ T cells and macrophages. The SD-56-day model group showed more severe inflammatory cells infiltration than SD-45-day model group. Moreover, inflammatory cells infiltration and red secretions in B6 model were less than SD model. Expression of CD4+ T cells and macrophages was also consistent with H&E results. These results indicated that different stages of CP/CPPS, inflammatory response, and the inflammation of the rat were stronger than the mouse. Our study suggests that CD4+ T cells and macrophages are key factors in the development of CP/CPPS.

Efficacy of acupuncture in the treatment of chronic prostatitis-chronic pelvic pain syndrome: a review of the literature.

Among one of the four category prostatitis, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the disease with unknown etiology and having 90-95% prevalence in prostatitis. CP/CPPS poses adverse psychological effects and weakens the quality of life (QoL) of the patients. Due to its multifactorial etiology, various types of treatment are available with different management efficacies. The conventional treatment like anti-inflammatory medications, antibiotics, and alpha-blockers have given the lack of verified efficacy that has turned the patients to alternative therapies such as acupuncture because of its efficacy, safety, and high compliance. Acupuncture is an alternative management accepted in several countries and is commonly used in traditional Chinese medicine for chronic pain. Acupuncture had the effect of immune modulation, anti-inflammatory, and neuromodulation. For chronic prostatitis, acupuncture can improve pain symptoms and can bring better results about National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and QoL. This review will discuss the efficacy of acupuncture in the treatment of CP/CPPS and effect of acupuncture on NIH-CPSI total score and its domains: pain, voiding, and QoL, as well as its effect on different biomarkers of CPPS.

Effect of Oral T2 Antigen on Chronic Prostatitis/Chronic Pelvic Pain Syndrome in Mice Model.

The exact etiology and pathogenesis of chronic prostatitis (CP/CPPS) remain unclear. However, autoimmunity is a widely known theory. Precise treatment of CP/CPPS is not available. Here, we developed a new effective treatment method to prevent the occurrence of CP/CPPS. A total of 40 male C57BL/6 mice were randomly divided into four groups (n = 10): i.e., naive, model, high-dose (500 µg/ml), and low-dose (50 µg/ml) groups. High-dose and low-dose groups were orally given 0.4 ml of T2-containing soybean trypsin inhibitor (STI) at once after every 2 days for a total of 10 days. On day 10 and day 24 all the groups except naïve group were subcutaneously injected with 0.2 ml of T2 peptide along with CFA to make valid CP/CPPS models. Hematoxylin and eosin staining were used to evaluate the variation in CP/CPPS manifestation. Voiding behavior was recorded for the evaluation of urine frequencies. ELISA was used to measure the serum level of TNF-α in each group. The high- and low-dose groups of T2-containing STI displayed a reduction in urine frequencies, and inflammation, and there was a slight inflammatory infiltration as compared to the model group. In contrast, there was no difference observed in the TNF-α concentration of model as well as high- and low-dose groups compared to the naïve group. Our study demonstrates that oral T2-containing STI prevents CP/CPPS and provides an effective approach for the treatment of CP/CPPS.

Interventions to chronic prostatitis/Chronic pelvic pain syndrome treatment. Where are we standing and what's next?

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frustrating syndrome. The pathogenesis and state of the art treatment of CP/CPPS are not known. A wide variety of therapies including anti-inflammatories, antibiotics, alpha-blockers, neuropathic pain modulators, and 5α-reductase inhibitors are in practice. These treatment strategies focus on alleviating symptoms in specific domains without treating root-cause and therapeutic outcome is far from satisfactory. We review the literature on current pharmacological treatments for CP/CPPS in detail and suggest future perspectives to modify the treatment strategies. We suggest that introducing novel treatment strategies such as gene editing, and Tregs expressing chimeric receptors may improve the treatment outcomes by inducing immune tolerance and controlling expression of pro-inflammatory cytokines.

Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway.

Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, the incidence of cardiotoxicity compromises its therapeutic index. Oxidative stress and apoptosis are believed to be involved in DOX-induced cardiotoxicity. Chitosan oligosaccharides (COS), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities including antioxidant and anti-apoptotic properties. The objective of the present study was to investigate the potential role of COS against DOX-induced cardiotoxicity, and the effects of COS on apoptosis and oxidative stress in rats and H9C2 cells. Furthermore, we also shed light on the involved pathways during the whole process. For this purpose, first, we demonstrated that COS exhibited a significant protective effect on cardiac tissue by not only inducing a decrease in body and heart growth but also ameliorated oxidative damage and ECG alterations in DOX-treated rats. Second, we found that COS reversed the decrease of cell viability induced by DOX, reduced the intracellular reactive oxygen species (ROS), increased the mitochondrial membrane potential (MMP) and Bcl-2/Bax ratio. COS treatment also results in reduced caspase-3 and caspase-9 expressions, and an increase in the phosphorylation of MAPKs (mitogen-activated protein kinases) in DOX-exposed H9C2 cells. Additionally, cellular homeostasis was re-established via stabilization of MAPK mediated nuclear factor erythroid 2-related factor 2/antioxidant-response element (Nrf2/ARE) signaling and transcription of downstream cytoprotective genes. In summary, these findings suggest that COS could be a potential candidate for the prevention and treatment of DOX-induced cardiotoxicity.

Novel Treatment of Experimental Autoimmune Prostatitis by Nanoparticle-Conjugated Autoantigen Peptide T2.

The exact etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still unknown, as a result, available therapeutic options for patients are far from satisfactory. Therefore, there is a need to develop a valid therapeutic approach that can ameliorate the manifestations of CP/CPPS. Fifty male C57BL/6 mice were randomly divided into five groups of ten mice each. All groups except naïve were subcutaneously injected with 0.2 ml of T2 plus complete Freund adjuvant (CFA) on day 0 and 14 to generate valid CP/CPPS model. After successful CP/CPPS induction, model group was injected with 0.2 ml of normal saline while PLGA, PLGA-OVA, and PLGA-T2 groups were administered intravenously with 0.2 ml mixture of PLGA, PLGA-OVA, and PLGA-T2, respectively. Voiding behavior, pain threshold, and hematoxylin and eosin staining were used to assess micturition habits, pain intensity as well as prostate inflammation. Additionally, TNF-α, CRP, and IL-10 levels in plasma were measured by using ELISA kits. Mice administered with PLGA-T2 showed higher pain threshold, lower urine frequencies, mild edema, and inflammation in prostate tissue in comparison to other groups. Moreover, the expression of TNF-α and CRP levels was markedly decreased while IL-10 expression was increased in the PLGA-T2 treatment group as compared to the other groups. Our results showed that nanoparticles conjugated with autoantigen novel peptide T2 could successfully alleviate or even heal CP/CPPS to some extent in mice. This study provides an easy, useful, and economic tool for ameliorating the manifestations of CP/CPPS that will improve the therapeutic approaches.

Chitosan oligosaccharide (COS): An overview.

The frequently studied polysaccharide, chitosan oligosaccharide/chitooligosaccharide (COS) is the major degradation product of chitosan/chitin via chemical hydrolysis or enzymatic degradation involving deacetylation and depolymerization processes. Innumerable studies have revealed in the recent decade that COS has various promising biomedical implications in the past analysis, current developments and potential applications in a biomedical, pharmaceutical and agricultural sector. Innovations into COS derivatization has broadened its application in cosmeceutical and nutraceutical productions as well as in water treatment and environmental safety. In relation to its parent biomaterials and other available polysaccharides, COS has low molecular weight (Mw), higher degree of deacetylation (DD), higher degree of polymerization (DP), less viscous and complete water solubility, which endowed it with significant biological properties like antimicrobial, antioxidant, anti-inflammatory and antihypertensive, as well as drug/DNA delivery ability. In addition, it is also revealed to exhibit antidiabetic, anti-obesity, anti-HIV-1, anti-Alzheimer's disease, hypocholesterolemic, calcium absorption and hemostatic effects. Furthermore, COS is shown to have higher cellular transduction and completely absorbable via intestinal epithelium due to its cationic sphere exposed on the more exposed shorter N-glucosamine (N-Glc) units. This paper narrates the recent developments in COS biomedical applications while paying considerable attention to its physicochemical properties and its chemical composition. Its pharmacokinetic aspects are also briefly discussed while highlighting potential overdose or lethal dosing. In addition, due to its multiple NGlc unit composition and vulnerability to degradation, its safety is given significant attention. Finally, a suggestion is made for extensive study on COS anti-HIV effects with well-refined batches.

A novel approach to devise the therapy for ventricular fibrillation by epicardial delivery of lidocaine using active hydraulic ventricular attaching support system: An experimental study in rats.

Active hydraulic ventricular attaching support system (ASD) placed around the heart is not only a novel, nontransplant surgical device used for epicardial administration of drugs like lidocaine, but also a promising treatment option for ventricular fibrillation (VF) and arrhythmias. We hypothesize that lidocaine in 5 mg/kg dose released by ASD significantly improves the VF in the rat model. Sprague-Dawley (SD) rats were selected and were divided into four groups, intravenous injection (IV), epicardial infusion (EI), ASD, and control. ASD group was further divided into four subgroups for different lidocaine doses (i) ASD+A group (10 mg/kg), (ii) ASD+B group (5 mg/kg), (iii) ASD+C group (1 mg/kg), and (iv) ASD+D group (0.1 mg/kg). VF was induced with calcium chloride injection and was confirmed by electrocardiogram (ECG) in all the groups. VF was treated with different doses of lidocaine using different modes of administration. Data were analyzed using the SPSS 19.0 Chi-square tests and one-way analysis of variance (ANOVA). The Kaplan-Meier curve for OS was compared to the Logrank test based on the survival time. P < 0.05 was considered as statistically significant. ASD + B group (5 mg/kg) showed significantly reduced sgroup. The time of first sinus rhythm recovered (15.96 ± 21.77 min) and ▵T-SOD in plasma (-42.02 ± 26.99 U/mL) was significantly different than that of control, IV, and EI groups. ▵T-SOD in plasma for all ASD-treated groups was smaller than the control and IV groups. This study proves that ASD with 5 mg/kg lidocaine dose appears as a promising therapeutic platform for treating VF in rats. Furthermore, ASD may also have potential for treating VF or other cardiovascular disease with different therapeutic agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1722-1731, 2019.

A nanoparticle-coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in mice model.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease of unclear etiology. Precise treatment of CP/CPPS is not available due to lack of specific cause; however, autoimmunity is the most valid theory. We develop a new treatment strategy that involves synthesis and coupling of biodegradable nanoparticles to antigenic T2 peptide to induce immune tolerance in CP/CPPS mice models. A total of 50 male C57BL/6 mice were randomized into five groups, that is, naïve, Model, PLGA-PEMA, PLGA-PEMA-OVA323-339 , and PLGA-PEMA-T2 group. All groups except naïve were injected subcutaneously on day 0 with 0.2 mL of T2 peptide with CFA to generate valid CP/CPPS models. After successful induction of CP/CPPS, Model group, PLGA-PEMA, PLGA-PEMA-OVA, and PLGA-PEMA-T2 groups were treated with 0.15 mL of normal saline, 0.2 mg of PLGA-PEMA and PLG-PEMA-T2 and 0.3 mg PLGA-PEMA-OVA nanoparticles, respectively, on day 28. Hematoxylin and eosin staining, and ELISA were used to evaluate the variation in CP/CPPS manifestations and seral level of IL-10 in each group. Pain threshold and voiding behavior were also recorded for every group. Mice treated with PLGA-PEMA-T2 exhibited enhanced pain threshold, reduced urine frequency, and prostate pathology. Furthermore, serum level of inflammatory mediators (TNF-α and CRP) were reduced and anti-inflammatory IL-10 was enhanced in PLGA-PEMA-T2 group as compared to other groups. Our results demonstrate that PLGA-PEMA-T2 nanoparticle ameliorates disease manifestations in CP/CPPS mice models and upregulates IL-10 which is essential for tolerance induction. This strategy highlights the new therapeutic approach utilizing biodegradable nanoparticles for the treatment of CP/CPPS.

Role of oxidative stress in pathology of chronic prostatitis/chronic pelvic pain syndrome and male infertility and antioxidants function in ameliorating oxidative stress.

Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body that can cause tissue damage. Oxidative stress has a significant involvement in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and male infertility. CP/CPPS is a major risk factor for male infertility due to generation of excessive ROS that damage sperm DNA, lipids, and proteins, resulting in compromised vitality and decreased sperm motility. Here we present a comprehensive review of oxidative stress relevance in CP/CPPS and male infertility, and embody the protective effects of antioxidants against ROS. An online literature was searched using the following keywords/terms: oxidative stress, ROS, Oxidative stress and chronic prostatitis, oxidative stress and male infertility and antioxidants. Original and review articles, clinical trials, and case reports of human and animal studies published till 2017 were searched using the PubMed and MEDLINE.

Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases.

Cardiovascular diseases (CVDs) are considered as the major reason for mortality and morbidity worldwide. Substantial evidence suggests that increased oxidative stress plays a significant role in the pathogenesis of CVDs, including atherosclerosis, hypertension, vascular endothelial dysfunction and ischemic heart disease. Cellular oxidative stress results in the release of toxic free radicals by endothelial cells and vascular smooth muscle cells that interact with cell components such as protein, DNA or lipid resulting in cardiovascular pathology. Silymarin has antioxidant activities against CVDs and offers protection against oxidative stress-induced hypertension, atherosclerosis and cardiac toxicity. We present a comprehensive review regarding the oxidative stress and protective effects of silymarin in CVDs management. We also aim to provide mechanistic insight of the mechanisms of silymarin action in oxidative stress-induced CVDs.