Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H2S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H2S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H2S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H2S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confirm that the polyherbal extract chandraprabha vati may be a useful therapy for inflammatory disorders by reducing H2S levels

Current advances of nitric oxide in cancer and anticancer therapeutics

Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer

Inhibition of cystathionine-γ-lyase-mediated hydrogen sulfide production in LPS-stimulated RAW 264.7 macrophages by polyherbal extract

111-117The polyherbal formulation chandraprabha vati (CV) comprising 29 herbs is traditionally used as an anti-inflammatory agent for arthritis and urinary ailments in Indian Siddha medicine. Earlier, we reported that lipopolysaccharide (LPS) induced apoptosis in RAW 264.7 macrophages is mediated by hydrogen sulfide (H2S), a potential target for many inflammatory diseases. Here, we hypothesized that pretreatment with CV decreases H2S level and thereby alleviate the inflammatory conditions induced by LPS in RAW 264.7 macrophages, and this protective effect occurs through alterations in cystathionine-γ-lyase (CSE), a H2S synthesizing enzyme. Accordingly, we evaluated the anti-inflammatory effect of CV in LPS-stimulated RAW 264.7 macrophages in vitro. The CV pretreatment followed by 12 h of LPS-stimulation showed significantly decreased TNF-α, H2S production possibly through CSE gene expression and NF-кB activation compared to the non pretreated macrophages. Our results further confirm that the polyherbal extract chandraprabha vati may be a useful therapy for inflammatory disorders by reducing H2S levels

The Use of HCG‐Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use

Introduction and AimAbout 3 million men take testosterone in the United States with many reproductive‐age men unaware of the negative impact of testosterone supplementation on fertility. Addressing this population, we provide an early report on the use of human chorionic gonadotropin (HCG)‐based combination therapy in the treatment of a series of men with likely testosterone‐related azoospermia or severe oligospermia. MethodsWe retrospectively reviewed charts from two tertiary care infertility clinics to identify men presenting with azoospermia or severe oligospermia (<1 million sperm/mL) while taking exogenous testosterone. All were noted to have been placed on combination therapy, which included 3,000 units HCG subcutaneously every other day supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant follicle‐stimulating hormone (or combination) according to physician preference.Main Outcome MeasureClinical outcomes, including hormone values, semen analyses, and clinical pregnancies, were tracked. ResultsForty‐nine men were included in this case series. Return of spermatogenesis for azoospermic men or improved counts for men with severe oligospermia was documented in 47 men (95.9%), with one additional man (2.1%) having a documented pregnancy without follow‐up semen analysis. The average time to return of spermatogenesis was 4.6 months with a mean first density of 22.6 million/mL. There was no significant difference in recovery by type of testosterone administered or supplemental therapy. No men stopped HCG or supplemental medications because of adverse events. ConclusionsWe here provide an early report of the feasibility of using combination therapy with HCG and supplemental medications in treating men with testosterone‐related infertility. Future discussion and studies are needed to further characterize this therapeutic approach and document the presumed improved tolerability and speed of recovery compared with unaided withdrawal of exogenous testosterone. Wenker EP, Dupree JM, Langille GM, Kovac J, Ramasamy R, Lamb D, Mills JN, and Lipshultz LI. The use of HCG‐based combination therapy for recovery of spermatogenesis after testosterone use. J Sex Med 2015;12:1334–1337.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111925/1/jsm12890.pd

Rare single gene disorders:estimating baseline prevalence and outcomes worldwide

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and service needs. Here, we present an approach to estimate the burden of these conditions up to 5 years of age in settings without empirical data. This approaches uses population-level demographic data, combined with assumptions based on empirical data from settings with data available, to provide population-level estimates which programmes and policy-makers when planning services can use

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause

Standards in semen examination:publishing reproducible and reliable data based on high-quality methodology

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.Peer reviewe

Primary Treatment of Peyronie’s Disease: A 55-yr-old Male with 45° Dorsal Penile Curvature and Good Erectile Function

Peyronie’s disease is an abnormal curvature of the penis that affects sexual intercourse. The treatment options include injection therapy into the scar or surgical correction of the curvature using plication or grafting