Association of Hormonal Contraceptives with Depression among Women in Reproductive Age Groups: A Cross-Sectional Analytic Study.

Introduction: Hormonal contraceptives (HCs) are used for birth control, menstrual disturbances, and premenopausal syndrome. Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Methods: A cross-sectional study was conducted on 326 women of the reproductive age group (15-49 years) attending the family planning unit of the obstetrics and gynecology department of a medical college in Saudi Arabia. Their sociodemographic and medical details along with the current use of any contraceptives (hormonal, nonhormonal, or not using any) with duration were collected. Beck depression inventory-II (BDI-II) was applied to the women to assess for depression along with its severity, and a BDI score of >16 was taken to denote clinical depression. Women were stratified by type of contraceptive used, and its association with depression category was assessed. Results: A total of 326 consenting eligible women in the age group of 15-49 years were enrolled in the study of which 165 (50.6%) were currently using a hormonal contraceptive and 49 (15.0%) were using a nonhormonal contraceptive and the rest 112 (34.4%) were not using any contraceptives. There was no significant difference in the mean BDI scores (p=0.79) and degrees of depression (p=0.06) between the HC users and HC nonusers. However, individual symptoms of depression such as sadness (p=0.01), reduced libido (p=0.0002), feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly higher in the HC users than non-HC users. Conclusion: We conclude that there was no significant difference in mean depression scores between groups. However, a few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

Targeting signaling pathways with andrographolide in cancer therapy (Review).

Terpenoids are a large group of naturally occurring organic compounds with a wide range of components. A phytoconstituent in this group, andrographolide, which is derived from a plant called Andrographis paniculate, offers a number of advantages, including anti-inflammatory, anticancer, anti-angiogenesis and antioxidant effects. The present review elucidates the capacity of andrographolide to inhibit signaling pathways, namely the nuclear factor-κB (NF-κB), hypoxia-inducible factor 1 (HIF-1), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Wnt/ß-catenin and mitogen-activated protein kinase (MAPK) pathways, which are involved in cellular processes and responses such as the inflammatory response, apoptosis and angiogenesis. Inhibiting pathways enables andrographolide to exhibit its anticancer effects against breast, colorectal and lung cancer. The present review focuses on the anticancer effects of andrographolide, specifically in breast, colorectal and lung cancer through the NF-κB, HIF-1 and JAK/STAT signaling pathways. Therefore, the Google Scholar, PubMed and ScienceDirect databases were used to search for references to these prevalent types of cancer and the anticancer mechanisms of andrographolide associated with them. The following key words were used: Andrographolide, anticancer, JAK/STAT, HIF-1, NF-κB, PI3K/AKT/mTOR, Wnt/ß-catenin and MAPK pathways, and the literature was limited to studies published between 2010 to 2023. The present review article provides details about the different involvements of signaling pathways in the anticancer mechanisms of andrographolide.

Pyridylpiperazine-based carbodithioates as urease inhibitors: synthesis and biological evaluation.

The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives 5a-5n and 7a-7n that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives 5a-5n and 7a-7n were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography-mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, 5j (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC50 value of 5.16 ± 2.68 µM. This IC50 value is notably lower than that of thiourea (23 ± 0.03 µM), indicating the significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified.

Treating Depression in Dementia Patients: A Risk or Remedy-A Narrative Review.

BACKGROUND: The diagnosis of depression in dementia patients leads to an increase in the burden of the disease. To treat depression in this patient group, antidepressants are frequently used; however, there is not any proof of their therapeutic effectiveness, and their use may be potentially harmful. This narrative review aims to summarize the existing evidence regarding the role of antidepressants in treating depression in dementia patients. MAIN TEXT: A search was conducted in the PubMed, Excerpta Medica database (EMBASE), and Cochrane databases for randomized controlled trials and meta-analyses wherein antidepressants were given to dementia sufferers to address depression. Fifteen randomized controlled trials and seven meta-analyses were identified. Most well-designed blinded placebo-controlled trials reported a lack of effectiveness of antidepressants in treating depression in dementia patients. Among the seven metanalyses, two reported good efficacy of Selective serotonin reuptake inhibitors (SSRIs). However, two major Cochrane reviews reported little or no effectiveness and increased side effects of antidepressants in dementia patients. CONCLUSION: There is robust evidence regarding the lack of efficacy of antidepressants in treating depression in dementia patients. However, further well-designed Randomized controlled trials (RCTs,) using scales with good validity and reliability to diagnose depression in dementia patients, sufficient sample sizes, and detailed adverse effect profiles may help determine the rationale for their use.

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors.

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of -8.0 (5b) and -8.1 (7e) kcal/mol. The binding energy of thiourea was -2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and -6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

Recent synthetic approaches towards thienothiophenes: a potential template for biologically active compounds.

Heterocyclic compounds are attractive candidates because of their vast applications in natural and physical sciences. Thienothiophene (TT) is an annulated ring of two thiophene rings with a stable and electron-rich structure. Thienothiophenes (TTs) fully represent the planar system, which can drastically alter or improve the fundamental properties of organic, π-conjugated materials when included into a molecular architecture. These molecules possessed many applications including, pharmaceutical as well as optoelectronic properties. Different isomeric forms of thienothiophene showed various applications such as antiviral, antitumor, antiglaucoma, antimicrobial, and as semiconductors, solar cells, organic field effect transistors, electroluminiscents etc. A number of methodologies were adopted to synthesize thienothiophene derivatives. In this review, we have addressed different synthetic strategies of various isomeric forms of thienothiophene that have been reported during last seven years, i.e., 2016-2022.

Prevalence of depression, anxiety, stress and its relationship with knowledge about COVID-19 in medical and laboratory medicine students of Umm-Al-Qura University: a cross-sectional survey.

Introduction: Coronavirus disease 2019 (COVID-19) pandemic has continued relentlessly for over one and half years now, causing a threat to life, fear of falling sick, helplessness, anxiety, depression and, pessimism about the future. There has been an increasing concern over student mental health in higher education. Our study was designed to measure current mental health status and its relationship with sociodemographic variables and level of knowledge about COVID-19 in Saudi Arabia. Method: A cross-sectional survey was conducted among laboratory medicine students of Makkah city, Saudi Arabia from October, 2020 to January, 21. A semi-structured questionnaire was circulated through mail and What's App. Data collected included sociodemographic details and level of knowledge towards the COVID-19 among the students. Depression anxiety and stress-21 item (DASS 21) was used to assess psychological status. Result: Our study reported 51.4% depressive symptoms, 57.9% anxiety symptoms, and 48.5% stress in the study participants. History of being hospitalized with COVID-19 and ICU reported high anxiety (p = 0.0003) and depression scores (p = 0.04). Respiratory droplet as a mode of transmission revealed higher scores on anxiety subscale (p = 0.007), whereas surface contamination reported high score of stress (p = 0.004) and anxiety (p = 0.002). Knowing that COVID-19 can also clinically present with gastrointestinal symptoms was found to show high stress (p = 0.005) and anxiety (p = 0.01) scores than any other way of clinical presentation. Conclusion: COVID-19 is likely to cause negative effect on the psychological health of students.

Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19.

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.

Identification of Cyclic Sulfonamides with an N-Arylacetamide Group as α-Glucosidase and α-Amylase Inhibitors: Biological Evaluation and Molecular Modeling.

Diabetes mellitus (DM), a complicated metabolic disorder, is due to insensitivity to insulin function or reduction in insulin secretion, which results in postprandial hyperglycemia. α-Glucosidase inhibitors (AGIs) and α-amylase inhibitors (AAIs) block the function of digestive enzymes, which delays the carbohydrate hydrolysis process and ultimately helps to control the postprandial hyperglycemia. Diversified 2-(3-(3-methoxybenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides were synthesized and evaluated for their in vitro inhibitory potential against α-glucosidase and α-amylase enzymes. The compounds with chloro, bromo and methyl substituents demonstrated good inhibition of α-glucosidase enzymes having IC50 values in the range of 25.88-46.25 µM, which are less than the standard drug, acarbose (IC50 = 58.8 µM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC50 values of 7.52 to 15.06 µM, lower than acarbose (IC50 = 17.0 µM). In addition, the most potent compound, N-(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetamide (12i), was found to be a non-competitive and competitive inhibitor of α-glucosidase and α-amylase enzymes, respectively, during kinetic studies. The molecular docking studies provided the binding modes of active compounds and the molecular dynamics simulation studies of compound 12i in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.

Neuroimaging changes associated with vitamin D Deficiency - a narrative review.

ABSTRACTEmerging evidence suggests the role of vitamin D in brain health and its implication in the pathogenesis of cognitive impairment. The Aim of this review is to summarize current evidence on neuroimaging changes seen in vitamin D deficient individuals. Cross-sectional and longitudinal studies have consistently found an association between low serum 25 hydroxyvitamin D and cognitive impairment. Furthermore, investigating the association between serum 25 hydroxyvitamin D and neuroimaging abnormalities could provide an insight into the potential mechanisms underlying the association with cognitive impairment. Animal studies have demonstrated structural changes in the cerebral cortex and hippocampus of vitamin D deficient mice. Neuroimaging studies of the brain have shown increased white matter hyperintensities in periventricular, cortical, and juxtacortical areas and grey matter atrophy of the hippocampus, anterior cingulate cortex, and left calcarine sulcus in elderly with vitamin D deficiency.