Endometriosis and infertility: the hidden link between endometritis, hormonal imbalances and immune dysfunctions preventing implantation!

Endometriosis is a chronic inflammatory condition affecting up to 10% of women of reproductive age and this, depending on its severity, very often leads to infertility. New research has shed light on the role of underlying endometritis due to the presence of inflammatory, non-oestrogen metabolising microbiome at the mucosal interface and this in turn leads to the activation of aggressive, non-tolerant immune cells in the endometrium. These immune cells require the presence of tolerance-inducing commensals such as Lactobacilli so as to allow the implantation of the fertilised egg.

Validation of high-throughput, semiquantitative solid-phase SARS coronavirus-2 serology assays in serum and dried blood spot matrices.

Serological assays for the detection of anti-SARS coronavirus-2 (SARS-CoV-2) antibodies are essential to the response to the global pandemic. A ligand binding-based serological assay was validated for the semiquantitative detection of IgG, IgM, IgA and neutralizing antibodies (nAb) against SARS-CoV-2 in serum. The assay demonstrated high levels of diagnostic specificity and sensitivity (85-99% for all analytes).

Investigation of CYP2B6, 3A4 and β-esterase interactions of Withania somnifera (L.) dunal in human liver microsomes and HepG2 cells.

Ethnopharmacological Relevance: Withania somnifera (L.) Dunal (Solanaceae) is a traditional herb, used in African indigenous systems of medicine for the treatment of various diseases (including HIV/AIDS and tuberculosis). The relevance of clinically significant interactions of Withania with ARVs and anti-TB drugs needs to be investigated.

Assessment of the Interaction Potential of (L.) Extracts on CYP2B6, 3A4, and Rifampicin Metabolism.

L. or basilicum is a common culinary herb, used as a traditional medicine for various medical conditions including HIV/AIDS and tuberculosis, in Africa. The objective of this study was to evaluate the effect of methanol, ethanol, aqueous and ethyl acetate extracts of the dried leaves and inflorescence of , on the activity of cytochrome P450 enzymes (CYPs) CYP2B6 and 3A4, as well as esterase-mediated metabolism of rifampicin to 25--desacetyl rifampicin (25ODESRIF).

B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin's lymphoma patients.

Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin's lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis.

Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients.

Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort.

Problem: The impact of metabolic syndrome (MetS) associated systemic inflammation on the male reproductive tract requires further investigation.

Method Of Study: A cross-sectional case-controlled study design consisting of a control group (n=32) and a MetS (n=42) group was used. Variables include MetS diagnostic criterion, serum C-Reactive Protein (CRP), routine semen analysis, spermatozoa mitochondrial membrane potential (MMP) and DNA fragmentation (DF), as well as TNF-α, IL-1β, IL6 and IL8 concentrations in serum and semen.

In Vitro Evaluation of Reversible and Time-Dependent Inhibitory Effects of Kalanchoe crenata on CYP2C19 and CYP3A4 Activities.

Kalanchoe crenata popularly known as "dog's liver" is used in most African countries for the treatment of chronic diseases such as diabetes, asthma and HIV/AIDS related infections. The evaluation of K. crenata for herb-drug interactions has not been reported.

The inhibitory activity of the extracts of popular medicinal herbs on CYP1A2, 2C9, 2C19 and 3A4 and the implications for herb-drug interaction.

Background: Studies have suggested an increasing practice of concurrent herb-drug consumption. One of the major clinical risks of such concomitant herb-drug use is pharmacokinetic herb-drug interaction (HDI). This is brought about by the ability of phytochemicals to inhibit or induce the activity of metabolic enzymes.

Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway.

1.This study investigated the mechanism underlying Echinacea-mediated induction of CYP1A2, CYP3A4 and MDR1 in terms of human pregnane X receptor (PXR) activation. 2.

Biomarkers of HIV-associated Cancer.

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy.

Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort.

Background: Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions.

Drug-drug interactions in HIV positive cancer patients.

Clinically relevant drug-drug interactions (DDIs) refer to the pharmacological or clinical response to the administration or co-exposure of a drug with another drug that modifies the patient's response. Treatment regimens, which include agents that are involved in the cytochrome P450 (CYP450) enzyme system and transporter systems, such as P-glycoprotein may be associated with higher risk of clinically significant drug interactions. In addition, potential DDIs increase with the increasing number of concomitant drugs.

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

Objectives: To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection.

Methods And Findings: Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination.

Inhibition of major drug metabolizing CYPs by common herbal medicines used by HIV/AIDS patients in Africa-- implications for herb-drug interactions.

The purpose of this study was to evaluate the potential risk of common herbal medicines used by HIV-infected patients in Africa for herb-drug interactions (HDI). High throughput screening assays consisting of recombinant Cytochrome P450 enzymes (CYPs) and fluorescent probes, and parallel artificial membrane permeability assays (PAMPA) were used. The potential of herbal medicines to cause HDI was ranked according to FDA guidelines for reversible inhibition and categorization of time dependent inhibition was based on the normalized ratio.

The potential of Hypoxis hemerocallidea for herb-drug interaction.

Context: Aqueous decoction of Hypoxis hemerocallidea Fisch. & C.A.

Effect of the metabolic syndrome on male reproductive function: a case-controlled pilot study.

The metabolic syndrome (MetS) is a constellation of various risk factors. This study aimed to investigate the effect of MetS on testosterone and progesterone, and semen parameters, in a case-controlled pilot study. Male patients (n = 54) had body mass index, waist-to-hip ratio (WHR) and blood pressure recorded.

The potential of Sutherlandia frutescens for herb-drug interaction.

In Africa, Sutherlandia frutescens is a popular medicinal herb widely consumed by people living with human immunodeficiency virus/AIDS. Concomitant use with antiretroviral drugs has generated concerns of herb-drug interaction (HDI). This study investigated the inhibitory effects of the crude extracts of S.

Plasma sarcosine does not distinguish early and advanced stages of prostate cancer.

Introduction: Diagnosis of prostate cancer by prostate specific antigen (PSA) is error-prone and cannot distinguish benign prostatic hyperplasia (BPH) from malignant disease, nor identify aggressive and indolent types.

Methods: We determined serum sarcosine (N-methylglycine) in 328 cancer patients by gas chromatography (GC)/mass spectroscopy (MS) and searched for correlations with early (stage T1/T2) and advanced (stage T3/T4) disease.

Results: Serum sarcosine of male control patients ranged from 1.

Interleukin-1α Induction in Human Keratinocytes (HaCaT): An In Vitro Model for Chemoprevention in Skin.

Long-term exposure to UV irradiation and toxic chemicals is associated with chronic inflammation that contributes to skin cancer development with interleukin-1 alpha (IL-1α), constitutively produced by keratinocytes, playing a pivotal role in skin inflammation. The aim of this study was to investigate the modulation of IL-1α production in the HaCaT keratinocyte cell line. Phorbol 12-myristate 13-acetate failed to induce IL-1α in HaCaT cells, and this might be associated with the specific deficiency known to affect downstream signalling of the MEK/ERK pathway in these cells.

An overview of the evidence and mechanisms of herb-drug interactions.

Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complementary medicine is globally popular. There is also an increasing interest in medicinal herbs as precursor for pharmacological actives. Of serious concern is the concurrent consumption of herbal products and conventional drugs.

Liver-based in vitro technologies for drug biotransformation studies - a review.

Early understanding of the metabolic pathway and potential interaction of new drug candidates with other drugs is one of the goals of preclinical studies in the drug discovery process. Although other body organs are involved in drug biotransformation, the liver is the predominant organ of metabolism for a wide range of endogenous compounds and xenobiotics. The set of enzymes contained in the cytochrome P450 superfamily present predominantly in the liver have been identified as the single most important agent of drug metabolism and have formed the bedrock of most matured technologies for in vitro drug biotransformation studies.

Lymphocyte measures in treatment-naïve 13-15-year old adolescents with alcohol use disorders.

Many adolescents have chronic exposure to hazardous levels of alcohol. This is likely to be a significant predictor of health outcomes, including those related to immunity. We assessed substance use and biochemical immunological parameters in heavy drinking adolescents (meeting DSM-IV criteria for alcohol dependence) and light/nondrinking control adolescents in Cape Town.

TUNEL assay and SCSA determine different aspects of sperm DNA damage.

For the determination of sperm DNA damage, different assays are used. However, no further distinction is made and the literature generally speaks about DNA damage. Thus, this study aimed at comparing the sperm chromatin structure assay (SCSA) and the TUNEL assay.

Permeation of four oral drugs through human intestinal mucosa.

The pharmaceutical industry is in need of rapid and accurate methods to screen new drug leads for intestinal permeability potential in the early stages of drug discovery. Excised human jejunal mucosa was used to investigate the permeability of the small intestine to four oral drugs, using a flow-through diffusion system. The four drugs were selected as representative model compounds of drug classes 1 and 3 according to the biopharmaceutics classification system (BCS).