Impact of Probiotics and Prebiotics on Gut Microbiome and Hormonal Regulation.

The gut microbiome plays a crucial role in human health by influencing various physiological functions through complex interactions with the endocrine system. These interactions involve the production of metabolites, signaling molecules, and direct communication with endocrine cells, which modulate hormone secretion and activity. As a result, the microbiome can exert neuroendocrine effects and contribute to metabolic regulation, adiposity, and appetite control.

MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.

Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity.

Novel arylidene-5(4H)-imidazolone derivatives 4a-r were designed and evaluated as multidrug-directed ligands, that is, inflammatory, proinflammatory mediators, and reactive oxygen species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). Compounds 4f, 4l, and 4p exhibited COX-2 selectivity comparable to that of celecoxib, while 4k was the most selective COX-2 inhibitor.

Biomarkers in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is diagnosed by the presence of two of the following three characteristics: hyperandrogenemia and/or hyperandrogenism, oligo/amenorrhea, and polycystic ovarian morphology. PCOS is associated with reproductive and non-reproductive complications, including obesity, insulin resistance and diabetes, dyslipidemia, and increased blood pressure.

Magic shotgun approach to anti-inflammatory pharmacotherapy: Synthesis of novel thienopyrimidine monomers/heterodimer as dual COX-2 and 15-LOX inhibitors endowed with potent antioxidant activity.

Emerging evidence points to the intertwining framework of inflammation and oxidative stress in various ailments. We speculate on the potential impact of the magic shotgun approach in these ailments as an attempt to mitigate the drawbacks of current NSAIDs. Hence, we rationally designed and synthesized new tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine monomers/heterodimer as dual selective COX-2/15-LOX inhibitors with potent antioxidant activity.

Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.

A new series of thieno[2,3-d]pyrimidine derivatives 4, 5, 6a-o, and 11 was designed and synthesized starting from cyclohexanone under Gewald condition with the aim to develop multitarget-directed ligands (MTDLs) having anti-inflammatory properties against both 15-LOX and COX-2 enzymes. Moreover, the potential of the compounds against the proinflammatory mediators NO, ROS, TNF-α, and IL-6 were tested in LPS-activated RAW 264.7 macrophages.

Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.

Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is recognized as the most common cause of ALF in Western societies. APAP-induced ALF is characterized by coagulopathy, hepatic encephalopathy, multi-organ failure, and death. MicroRNAs are small, non-coding RNAs that regulate gene expression at the post-transcriptional level.

Triple targeting of mutant EGFR, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation.

We designed and synthesised novel quinazolinone tethered phenyl urea derivatives () that triple target the double mutant EGFR, COX-2, and 15-LOX. Compounds (, , , , and ) not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1 and for EGFR over wild-type EGFR. Except for and , all of the tested compounds inhibited the NO production significantly more potently than celecoxib, diclofenac, and indomethacin.

Obesity-associated cardiometabolic complications in polycystic ovary syndrome: The potential role of sodium-glucose cotransporter-2 inhibitors.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by androgen excess, oligo/anovulation, and polycystic appearance of the ovaries. Women with PCOS have an increased prevalence of multiple cardiovascular risk factors such as insulin resistance, hypertension, renal injury, and obesity.

Sodium-Glucose Cotransporter-2 Inhibition Benefits in Cardiorenal Risk in Men and Women.

Introduction: In addition to their antihyperglycemic action, sodium-glucose cotransporter-2 (SGLT2) inhibitors are used in patients with type 2 diabetes due to their cardioprotective effects. Meta-analyses of large clinical trials have reported mixed results when examining sex differences in their cardioprotective effects. For example, some studies reported that, compared to women, men had a greater reduction in cardiovascular risk with SGLT2 inhibition.

Polycystic Ovary Syndrome: Insights from Preclinical Research.

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Inhibition of the ATR agonistic autoantibody in a rat model of preeclampsia improves fetal growth in late gestation.

Placenta ischemia, the initiating event in preeclampsia (PE), is associated with fetal growth restriction. Inhibition of the agonistic autoantibody against the angiotensin type 1 receptor AT-AA, using an epitope-binding inhibitory peptide ('n7AAc') attenuates increased blood pressure at gestational day (G)19 in the clinically relevant reduced uterine perfusion pressure (RUPP) model of PE. Thus we tested the hypothesis that maternal administration of 'n7AAc' does not transfer to the fetus, improves uterine blood flow and fetal growth, and attenuates elevated placental expression of miRNAs implicated in PE and FGR.

Mitochondrial function and oxidative stress in white adipose tissue in a rat model of PCOS: effect of SGLT2 inhibition.

Background: Polycystic ovary syndrome (PCOS), characterized by androgen excess and ovulatory dysfunction, is associated with a high prevalence of obesity and insulin resistance (IR) in women. We demonstrated that sodium-glucose cotransporter-2 inhibitor (SGLT2i) administration decreases fat mass without affecting IR in the PCOS model. In male models of IR, administration of SGLT2i decreases oxidative stress and improves mitochondrial function in white adipose tissue (WAT).

Design and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages.

In an attempt to obtain new candidates with potential anti-inflammatory activity, two series of 1,3,4-oxadiazole based derivatives (8a-g) and 1,2,4-triazole based derivatives (10a,b and 11a-g) were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. In vitro assays showed potent COX-2 inhibitory activity and selectivity of the novel designed compounds (IC = 0.04 - 0.

Management of cardiometabolic complications in polycystic ovary syndrome: Unmet needs.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and the most common cause of androgen excess in reproductive-age women. The heterogeneity of the clinical presentation in PCOS patients suggests the involvement of multiples abnormal physiological pathways. In addition, women with PCOS have a high prevalence of cardiometabolic risk factors.

Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19.

The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS.

Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities.

Novel quinazolinones conjugated with indole acetamide , ibuprofen ( or thioacetohydrazide ( and ) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID analogue and had equipotent COX-2 selectivity as celecoxib. Compared with celecoxib, , , and showed similar anti-inflammatory activity , while and showed superior inhibition of the inflammatory mediator nitric oxide, and showed greater antioxidant potential in macrophages cells.

SARS-CoV-2 Viral Entry Proteins in Hyperandrogenemic Female Mice: Implications for Women with PCOS and COVID-19.

SARS-CoV-2, the causative agent of COVID-19, infects host cells using the angiotensin I converting enzyme 2 (ACE2) as its receptor after priming by host proteases, including TMPRSS2. COVID-19 affects multiple organ systems, and male patients suffer increased severity and mortality. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women and is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.

Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition.

Based on the observed pharmacophoric structural features for the reported dual COX/15-LOX inhibitors and inspired by the abundance of COX/LOX inhibitory activities reported for the 1,2,4-triazine and quinoline scaffolds, we designed and synthesized novel 1,2,4-triazine-quinoline hybrids (8a-n). The synthesized hybrids were evaluated in vitro as dual COXs/15-LOX inhibitors. The new triazine-quinoline hybrids (8a-n) exhibited potent COX-2 inhibitory profiles (IC = 0.

Novel biomarkers of childhood and adolescent obesity.

Regulation of the Renin-Angiotensin System (RAS) and the kallikrein-kinin system (KKS) by obesity in adolescents. [Image: see text]