Role of mineral nutrients other than iron in pregnancy: under recognized opportunities to improve maternal/fetal outcomes: a literature review.

BACKGROUND: Anemia during pregnancy is an important global health concern, affecting 40% of women worldwide, and iron deficiency shares a significant proportion of the burden. From conception to birth, pregnancy is a period when women undergo metabolic and physiological changes. The nutritional needs are higher during pregnancy; thus, adequate nutrition is essential to maintain fetal growth and development. However, adverse effects due to deficiency in nutrition during pregnancy can result in maternal, fetal and neonatal complications. Despite the multifactorial etiology of anemia, iron deficiency is assumed as the primary cause of anemia during pregnancy and hence, mitigation strategy pivots around it for anemia management. Therefore, excluding other contributors, a single-micronutrient approach with iron supplements remains a myopic approach and this can exacerbate iron deficiency anemia. Micronutrient deficiencies are of particular concern as they may pose a silent threat to the survival and well-being of reproductive-age women and their infants. AIM: Micronutrients, especially trace minerals, play a myriad of roles in pregnancy, and the lack of each one causes adverse complications to both the mother and the fetus. In this review paper, we attempt to piece together available information regarding the adverse effects of abnormal trace mineral levels along with iron deficiency on the mother and the fetus. METHOD: A non-systematic literature search in PubMed, Google Scholar, and the Cochrane databases, for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcomes. CONCLUSION: Micronutrient deficiency exacerbates the pregnancy-induced anemia and other adverse birth outcomes. Micronutrient supplementation during pregnancy can combat anemia as well as reduce a number of adverse pregnancy outcomes in a comprehensive manner.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma.

Globally the incidence of hepatocellular carcinoma (HCC) is on an upsurge. Evidence is accumulating that liver disorders like nonalcoholic fatty liver disease (NAFLD) and its more progressive form nonalcoholic steatohepatitis (NASH) are associated with increased risk of developing HCC. NAFLD has a prevalence of about 25% and 50%-90% in obese population. With the growing burden of obesity epidemic worldwide, HCC presents a major healthcare burden. While cirrhosis is one of the major risk factors of HCC, available literature suggests that NAFLD/NASH associated HCC also develops in minimum or noncirrhotic livers. Therefore, there is an urgent need to understand the pathogenesis and risk factors associated with NAFLD and NASH related HCC that would help in early diagnosis and favorable prognosis of HCC secondary to NAFLD. Adipokines, hepatokines and myokines are factors secreted by adipocytes, hepatocytes and myocytes, respectively, playing essential roles in cellular homeostasis, energy balance and metabolism with autocrine, paracrine and endocrine effects. In this review, we endeavor to focus on the role of these organokines in the pathogenesis of NAFLD/NASH and its progression to HCC to augment the understanding of the factors stimulating hepatocytes to acquire a malignant phenotype. This shall aid in the development of novel therapeutic strategies and tools for early diagnosis of NAFLD/NASH and HCC.

NLRP3 inflammasome and bruton tyrosine kinase inhibition interferes with upregulated platelet aggregation and in vitro thrombus formation in sickle cell mice.

The nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) inflammasome is a critical inflammatory mechanism identified in platelets, which controls platelet activation and aggregation. We have recently shown that the platelet NLRP3 inflammasome is upregulated in sickle cell disease (SCD), which is mediated by Bruton tyrosine kinase (BTK). Here, we investigated the effect of pharmacological inhibition of NLRP3 and BTK on platelet aggregation and the formation of in vitro thrombi in Townes SCD mice. Mice were injected for 4 weeks with the NLRP3 inhibitor MCC950, the BTK inhibitor ibrutinib or vehicle control. NLRP3 activity, as monitored by caspase-1 activation, was upregulated in platelets from SCD mice, which was dependent on BTK. Large areas of platelet aggregates detected in the liver of SCD mice were decreased when mice were treated with MCC950 or ibrutinib. Moreover, platelet aggregation and in vitro thrombus formation were upregulated in SCD mice and were inhibited when mice were subjected to pharmacological inhibition of NLRP3 and BTK. Targeting the NLRP3 inflammasome might be a novel approach for antiplatelet therapy in SCD.

Global scenario of counterfeit antimalarials: A potential threat.

Malaria, a parasitic infectious disease causes approximately >1 million deaths annually worldwide. Treatment with effective antimalarials is one of the major strategies to combat malaria-related mortalities. However, there is a continuous threat of counterfeit antimalarials in the community. Counterfeit antimalarial drugs not only result in an economic loss but also decrease the efficacy of treatment resulting in the loss of faith in the health system and increases the the chances of drug resistance in the parasites. Counterfeit drugs hamper the intellectual property-based innovation paradigms as well. Awareness about these counterfeit drugs not only helps in avoiding drug resistance but may also enhance the drug therapeutic value. This review discusses the prevalence of counterfeit drugs in different geographic areas across the globe, the methods deployed for its detection and possible anticounterfeiting strategies. Literature search was conducted through PubMed, Google and International Pharmaceutical Abstracts using the terms 'counterfeit antimalarials', 'substandard', 'falsified', and 'drug resistance'. Free searches in other search engines included the terms 'antimalarial counterfeit drugs' and 'drug resistance'. Analysis of the literature survey indicated that majority of such studies were conducted in Southeast Asia and Africa region. The prevalence of substandard antimalarials was reported as high as 88.4% in Africa region and 53 % in Southeast Asia region. There is a need to follow a multifaceted approach to prevent the entry of falsified drugs with pre- and post-marketing surveillance. The samples need to be examined by regulatory bodies and strict legislation should be envisaged in order to maintain the quality of medicines.

Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction.

Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics, and long acting prostacyclin analog, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH. Understanding precise molecular cascade involved in PH can be useful for designing preclinical animal experiments and human clinical trials to evaluate target specific novel therapeutic interventions for the treatment of PH. In this review, we discussed the possible molecular signaling involved in the pathogenesis of PH and detailed account of the current status of medications employed for the treatment of PH. Moreover, the newly identified potential target sites and alternative approaches for treating the PH have been discussed.

Adropin may regulate ovarian functions by improving antioxidant potential in adult mouse.

The corpus luteum (CL) is a temporary endocrine gland that synthesizes progesterone. The luteal progesterone plays a central role in the regulation of the estrous cycle as well as the implantation and maintenance of pregnancy. Our previous study showed the expression of adropin and its receptor, GPR19, in the luteal cells and its significant role in luteinization. The aim of the present study was to investigate the in vitro effect of adropin on hCG-induced ovarian functions in adult mice. We also evaluated the effect of exogenous treatment with adropin on ovarian steroidogenesis and anti-oxidant parameters, with special emphasis on CL function. Our results demonstrated that adropin acts synergistically with hCG to promote ovarian steroidogenesis and survival by increasing the expression of StAR, 3ß-HSD, and aromatase proteins and decreasing the BAX/BCL2 ratio. Exogenous adropin treatment increased progesterone production by increasing the expression of GPR19, StAR and 3ß-HSD enzymes in the mouse ovary. Also, adropin inhibited the luteal oxidative stress by increasing nuclear translocation of NRF-2 in CL, which resulted in increased HO-1 expression and SOD, catalase activity. Decreased oxidative stress might inhibit the translocation of NF-κB into the nucleus of luteal cells, resulting into increased survival and decreased apoptosis, as evident by decreased lipid peroxidation, BAX/BCL2 ratio, caspase 3, active caspase 3 expression, and TUNEL-positive cells in adropin treated mice. Our findings suggest that adropin can be a promising candidate that can enhance the survivability of the CL.

Assessing the impact and mechanisms of environmental pollutants (heavy metals and pesticides) on the male reproductive system: a comprehensive review.

The escalation of technological advancements, coupled with the increased use of hazardous chemicals, has emerged as a significant concern for human health. Exposure to environmental pollutants like heavy metals and pesticides (insecticides, herbicides and fungicides) is known to significantly contribute to various health problems, particularly affecting reproductive health. Disturbances in reproductive potential and reproductive toxicity in males are particularly worrisome. Existing literature suggests that exposure to these environmental pollutants significantly alters male reproductive parameters. Thus, it is imperative to thoroughly analyze, comprehend, and evaluate their impact on male reproductive toxicity. Oxidative stress and disruptions in redox equilibrium are major factors through which these pollutants induce changes in sperm parameters and affect the reproductive system. Insecticides, fungicides, and herbicides act as endocrine disruptors, interfering with the secretion and function of reproductive hormones such as testosterone and luteinizing hormone (LH), consequently impacting spermatogenesis. Additionally, heavy metals are reported to bio-accumulate in reproductive organs, acting as endocrine disruptors and triggering oxidative stress. The co-operative association of these pollutants can lead to severe damage. In this comprehensive review, we have conducted an in-depth analysis of the impact of these environmental pollutants on the male reproductive system, shedding light on the underlying mechanisms of action.

Unveiling the Role of Artificial Intelligence (AI) in Polycystic Ovary Syndrome (PCOS) Diagnosis: A Comprehensive Review.

Polycystic Ovary Syndrome (PCOS) is one of the most widespread endocrine and metabolic disorders affecting women of reproductive age. Major symptoms include hyperandrogenism, polycystic ovary, irregular menstruation cycle, excessive hair growth, etc., which sometimes may lead to more severe complications like infertility, pregnancy complications and other co-morbidities such as diabetes, hypertension, sleep apnea, etc. Early detection and effective management of PCOS are essential to enhance patients' quality of life and reduce the chances of associated health complications. Artificial intelligence (AI) techniques have recently emerged as a popular methodology in the healthcare industry for diagnosing and managing complex diseases such as PCOS. AI utilizes machine learning algorithms to analyze ultrasound images and anthropometric and biochemical test result data to diagnose PCOS quickly and accurately. AI can assist in integrating different data sources, such as patient histories, lab findings, and medical records, to present a clear and complete picture of an individual's health. This information can help the physician make more informed and efficient diagnostic decisions. This review article provides a comprehensive analysis of the evolving role of AI in various aspects of the management of PCOS, with a major focus on AI-based diagnosis tools.

Emerging pollutants in etiology and pathophysiology of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder affecting reproductive-aged women worldwide. Although genetic and lifestyle factors have been implicated in its etiology, emerging evidence suggests that exposure to environmental pollutants may also contribute significantly to the development and pathophysiology of PCOS. This review article aims to provide a comprehensive overview of the potential role of emerging pollutants, including pharmaceuticals and personal care products (PPCPs), microplastics, endocrine disruptors, and nanoparticles, in PCOS development. The article summarizes the current understanding of PCOS pathogenesis and its clinical manifestations. Subsequently, it delves into the mechanisms of action of the emerging pollutants, exploring how they may disrupt the endocrine system, interfere with hormonal regulation, and contribute to the manifestation of PCOS symptoms. Moreover, the potential for cumulative effects and synergistic interactions between these pollutants demands a cautious approach when considering their role in PCOS etiology.

Implication of biosignatures in the progression of endometriosis.

Endometriosis is an estrogen-dependent chronic inflammatory disorder involving the placement and growth of endometrial tissue outside the uterine cavity. It is the most common multifactorial disease that affects the life quality of women in reproductive age. Due to its multicomponent nature, early diagnosis of the disease is challenging. Since many genetic, epigenetic alterations and non-genetic factors contribute to the pathology of endometriosis, devising a drug therapy that directly acts on the ectopic tissue is extremely difficult. Endometriosis is a hormone-driven disease with estrogen considered as a primary driver for the development of endometriotic lesions. This study aims to identify biosignatures involved in endometriosis with and without gonadotropin releasing hormone agonists (GnRHa). GnRHa is a short peptide analog of GnRH that causes inhibition of estrogen and androgen synthesis. Microarray based-gene expression profiling was performed on total RNA extracted from endometriotic tissue samples with and without GnRHa-treated patients already published in our previous paper. The untreated group were considered as the control. Genes were then selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis confirmed significant downregulation in(p < 0.05) expression of DARC (p = 0.0042), CDH1 (p = 0.0027), CDH5 (p = 0.0283), ATP2A3 (p < 0.001), RGS5 (p = 0.0032), and CD36 (p = 0.0162) in endometriosis patients treated with GnRHa analogs. Although, CTNNAL1 (p = 0.0136) also showed significant results but there was upregulation in their expression levels after GnRHa treatment. Thus, an altered expression of these genes makes them a possible candidate determinant of endometriosis treated with GnRHa.

Technological Interventions Enhancing Curcumin Bioavailability in Wound-Healing Therapeutics.

Wound healing has been a challenge in the medical field. Tremendous research has been carried out to expedite wound healing by fabricating various formulations, some of which are now commercially available. However, owing to their natural source, people have been attracted to advanced formulations with herbal components. Among various herbs, curcumin has been the center of attraction from ancient times for its healing properties due to its multiple therapeutic effects, including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, neuroprotective, and radioprotective properties. However, curcumin has a low water solubility and rapidly degrades into inactive metabolites, which limits its therapeutic efficacy. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, and keep its bioavailability and effectiveness. Different formulations with curcumin have been synthesized, and exist in the form of various synthetic and natural materials, including nanoparticles, hydrogels, scaffolds, films, fibers, and nanoemulgels, improving its bioavailability dramatically. This review discusses the advances in different types of curcumin-based formulations used in wound healing in recent times, concentrating on its mechanisms of action and discussing the updates on its application at several stages of the wound healing process. Impact statement Curcumin is a herbal compound extracted from turmeric root and has been used since time immemorial for its health benefits including wound healing. In clinical formulations, curcumin shows low bioavailability, which mainly stems from the way it is delivered in the body. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, while maintaining its bioavailability and therapeutic efficacy. This review offers an overview of the advanced technological interventions through tissue engineering approaches to efficiently utilize curcumin in different types of wound healing applications.

Molecular and functional characterization of cynomolgus monkey IgG subclasses.

Studies for vaccine and human therapeutic Ab development in cynomolgus monkeys (cynos) are influenced by immune responses, with Ab responses playing a significant role in efficacy and immunogenicity. Understanding the nature of cyno humoral immune responses and characterizing the predominant cyno IgG types produced and the Fc-FcγR interactions could provide insight into the immunomodulatory effects of vaccines. Anti-drug Ab responses against human IgG therapeutic candidates in cynos may affect efficacy and safety assessments because of the formation of immune complexes. There is, however, limited information on the structure and function of cyno IgG subclasses and how they compare with human IgG subclasses in Fc-dependent effector functions. To analyze the functional nature of cyno IgG subclasses, we cloned four cyno IgG C regions by using their sequence similarity to other primate IgGs. The four clones, cyno (cy)IGG1, cyIGG2, cyIGG3, cyIGG4, were then used to construct chimeric Abs. The sequence features of cyno IgG subclasses were compared with those of rhesus monkey and human IgG. Our data show that rhesus monkey and cyno IgG C regions are generally highly conserved, with differences in the hinge and hinge-proximal CH2 regions. Fc-dependent effector functions of cyno IgG subclasses were assessed in vitro with a variety of binding and functional assays. Our findings demonstrate distinctive functional properties of cyno IgG subclasses. It is notable that human IgG1 was less potent than cyno IgG1 in cyno FcγR binding and effector functions, with the differences emphasizing the need to carefully interpret preclinical data obtained with human IgG1 therapeutics.

Adropin may regulate corpus luteum formation and its function in adult mouse ovary.

BACKGROUND: Adropin, a unique peptide hormone, has been associated with the regulation of several physiological processes, including glucose homeostasis, fatty acid metabolism, and neovascularization. However, its possible role in ovarian function is not understood. Our objective was to examine the expression of adropin and its putative receptor, GPR19, in the ovaries of mice at various phases of the estrous cycle. METHODS: Immunohistochemistry and western blot analysis were performed to explore the localization and changes in expression of adropin and GPR19 in the ovaries during different phases of the estrous cycle in mice. Hormonal assays were performed with ELISA. An in vitro study was performed to examine the direct effect of adropin (10, 100 ng/ml) on ovarian function. RESULTS: A western blot study showed that adropin and GPR19 proteins were maximum during the estrus phase of the estrous cycle. Interestingly, adropin and GPR19 displayed intense immunoreactivity in granulosa cells of large antral follicles and corpus luteum. This suggested the possible involvement of adropin in corpus luteum formation. Adropin treatment stimulated progesterone synthesis by increasing GPR19, StAR, CYP11A1, and 3ß-HSD expressions, while it decreased estrogen synthesis by inhibiting 17ß-HSD and aromatase protein expressions. Moreover, adropin treatment upregulated the cell cycle arrest-CDK inhibitor 1B (p27kip1), pERK1/2, and angiogenic protein (EG VEGF) that are involved in the process of luteinization. CONCLUSIONS: Adropin GPR19 signaling promotes the synthesis of progesterone and upregulates the expression of p27kip1, EG VEGF, and erk1/2, resulting in cell cycle arrest and neovascularization, which ultimately leads to corpus luteum formation.

Critical review on emerging health effects associated with the indoor air quality and its sustainable management.

Indoor air quality (IAQ) is one of the fundamental elements affecting people's health and well-being. Currently, there is a lack of awareness among people about the quantification, identification, and possible health effects of IAQ. Airborne pollutants such as volatile organic compounds (VOCs), particulate matter (PM), sulfur dioxide (SO2), carbon monoxide (CO), nitrous oxide (NO), polycyclic aromatic hydrocarbons (PAHs) microbial spores, pollen, allergens, etc. primarily contribute to IAQ deterioration. This review discusses the sources of major indoor air pollutants, molecular toxicity mechanisms, and their effects on cardiovascular, ocular, neurological, women, and foetal health. Additionally, contemporary strategies and sustainable methods for regulating and reducing pollutant concentrations are emphasized, and current initiatives to address and enhance IAQ are explored, along with their unique advantages and potentials. Due to their longer exposure times and particular physical characteristics, women and children are more at risk for poor indoor air quality. By triggering many toxicity mechanisms, including oxidative stress, DNA methylation, epigenetic modifications, and gene activation, indoor air pollution can cause a range of health issues. Low birth weight, acute lower respiratory tract infections, Sick building syndromes (SBS), and early death are more prevalent in exposed residents. On the other hand, the main causes of incapacity and early mortality are lung cancer, chronic obstructive pulmonary disease, and cardiovascular disorders. It's crucial to acknowledge anticipated research needs and implemented efficient interventions and policies to lower health hazards.

Biomarkers of endometriosis.

Endometriosis is one of the most severe female reproductive disorders, affecting 6-10% of women between 18 and 35. It is a gynaecological condition where endometrial tissue develops and settles outside the uterus. The aetiology of endometriosis is primarily influenced by genetic, epigenetic, and non-genetic variables, making it highly challenging to create a therapeutic therapy explicitly targeting the ectopic tissue. The delay in the treatment is due to the limitations in the diagnostic approaches, which are restricted to invasive techniques such as laparoscopy or laparotomy. This accords to 70% of the women being diagnosed at later stages. By understanding the subject, several treatment medications have been produced to lessen the disease's symptoms. Nevertheless, endometriosis cannot be permanently cured. A viable or persuasive standard screening test for endometriosis must be utilized in a clinical context. A helpful assessment method for the early identification of endometriosis could be biomarkers. A major research priority is the identification of a biomarker that is sensitive and specific enough for detecting endometriosis. The present article has reviewed studies published on the expression of biomarkers of endometriosis. It outlines various biomarkers from different sample types, such as serum/plasma and urine, in addition to tissue. This would provide a non-invasive approach to diagnosing the disease at the initial stages without any harmful repercussions. Future high-throughput advances in science and technology are anticipated to result in the creation of a potent remedy for endometriosis. To achieve successful outcomes, it is necessary to research the discussed biomarkers that demonstrate substantial results extensively.

Demonstration of Physicochemical and Functional Similarity of Biosimilar Adalimumab-aqvh to Adalimumab.

BACKGROUND: Adalimumab-aqvh/CHS-1420 (YUSIMRYTM) (hereafter referred to as adalimumab-aqvh) was recently approved by the US Food and Drug Administration as a biosimilar for adalimumab. OBJECTIVE: The current study was conducted to investigate the analytical similarity of adalimumab-aqvh and the reference product, adalimumab. METHODS: The structural, functional, and stability attributes of adalimumab-aqvh and adalimumab were compared using state-of-the-art assays. The primary structure, disulfide structure, glycan profile, secondary and tertiary structures, molar mass, size variants, free thiol, charge variants, hydrophobic variants, post-translational modifications, subvisible particles, host cell proteins, and protein concentration were investigated. The functional similarity between adalimumab-aqvh and adalimumab was demonstrated by comparing fragment antigen-binding (Fab)-associated and fragment crystallizable (Fc)-associated biological activities. The stability of adalimumab-aqvh and of adalimumab was compared through forced degradation. RESULTS: The structural attributes of adalimumab-aqvh were identical to those of adalimumab or met the similarity criteria, with a few exceptions. Adalimumab-aqvh and adalimumab exhibited comparable stability profiles and functional activities. Any observed differences in the physiochemical attributes did not impact the conclusion of similarity because they did not influence any functional activities related to the adalimumab mechanism of action. CONCLUSION: The structural, functional, and stability data provide convincing evidence of biosimilarity between adalimumab-aqvh and the reference product, adalimumab.

Individualized lifestyle intervention in PCOS women (IPOS): a study protocol for a multicentric randomized controlled trial for evaluating the effectiveness of an individualized lifestyle intervention in PCOS women who wish to conceive.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine condition which affects women in the reproductive age group. South Asian women with PCOS have a higher risk of insulin resistance and metabolic disorder compared to women from other ethnic backgrounds. Lifestyle interventions such as dietary advice and physical exercise are recommended as a first-line management option for infertile women with PCOS. Most of the randomized controlled trials evaluating the role of lifestyle interventions in infertile PCOS women were characterized by methodological issues. The uptake of lifestyle modifications as a treatment strategy in the South Asian population is complicated by a difficult-to-change conventional high-carbohydrate diet and limited availability of space for physical activity in the region. METHODS: The study is designed as an open-label, multicentre, randomized controlled trial in South Asian women with PCOS. Women attending the fertility clinic will be screened for eligibility, and women aged between 19 and 37 years who have been diagnosed with PCOS and wishing to conceive will be invited to participate in the trial. We will include women with body mass index (BMI) between ≥ 23 and ≤ 35 kg/m2 and duration of infertility ≤ 3 years. We plan to randomize women with PCOS into two groups: group A will receive the intervention which will consist of individualized advice on diet and physical exercise along with a telephonic reminder system and follow-up visits, and group B (control) will receive one-time advice on diet and physical exercise. Both groups will receive up to three cycles of ovulation induction with letrozole after 3 months of randomization during the 6-month treatment period. The primary outcome of the trial will be the live birth following conception during the intervention period. The secondary outcomes include clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, ectopic pregnancy rate, stillbirth, time to pregnancy, mean weight loss, differences in anthropometric parameters, improvement in menstrual regularity and quality of life score. DISCUSSION: The IPOS trial results could help clarify and provide more robust evidence for advocating an individualized lifestyle intervention in PCOS women who wish to conceive. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2023/04/051620. Registered on 13 April 2023.

Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials.

Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections. To address the issue of regular injection, we have synthesized a fat fighting oral nano-formulation of liraglutide with a sustained release feature, which was evaluated against high fat diet (HFD) induced obesity in mice. Experimental obesity was induced in mice by feeding HFD for 26 weeks. Lir nanoparticles (NP) were fabricated with chitosan via ion-gelation technique and were coated with Eudragit@S100 to protect the drug in harsh gastric conditions. Physiochemical characterization of Eu-Lir-Cs-NP demonstrated a small particle size of 253.1 ± 1.21 nm with âˆ¼ 9.74 % loading and âˆ¼ 72.11 % encapsulation efficiency of the drug. In-vitro studies showed successful cellular uptake of NP in Caco-2 cells and were stable in various enteric fluid pH conditions. Eudragit@S100 coated chitosan NP were able to protect the drug from harsh gastric pH conditions with more than âˆ¼ 74% of recovery. Treatment of two weeks of liraglutide Eu-Lir-Cs-NP (0.1, 0.2 and 0.4 mg/kg, orally; twice daily) moderately reduces obesity in mice as evidenced by a reduction in the body weight, blood glucose, serum total cholesterol, serum triglyceride, serum resistin and serum insulin level of mice. In addition, significant reduction of liver weight, abdominal white adipose tissue, and hepatic oxidative stress were noted. Our results suggest that chitosan-based NP of liraglutide can be an effective and convenient formulation for the management of obesity.

Assessment of MMP14, CAV2, CLU and SPARCL1 expression profiles in endometriosis.

Endometriotic cells exhibit a notable degree of invasiveness and some characteristics of tissue remodeling underlying lesion formation. In this regard, do matrix metalloproteinases 14 (MMP14) and other related genes such as SPARC-like protein 1 (SPARCL1), caveolin 2 (CAV2), and clusterin (CLU) exert any significant influence in the processes of endometriosis development and pathophysiology is not apparent. We aim to assess whether these genes could serve as potential diagnostic biomarkers in endometriosis. Microarray-based gene expression analysis was performed on total RNA extracted from endometriotic tissue samples treated with and without gonadotropin-releasing hormone agonist (GnRHa). The GnRHa untreated patients were considered the control group. The validation of genes was performed using quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis showed significant downregulation in the expression of MMP14 (p = 0.024), CAV2 (p = 0.017), and upregulation of CLU (p = 0.005) in endometriosis patients treated with GnRHa. SPARCL1 did not show any significant (p = 0.30) change in the expression compared to the control group. These data have the potential to contribute to the comprehension of the molecular pathways implicated in the remodeling of the extracellular matrix, which is a vital step for the physiology of the endometrium. Based on the result, it is concluded that changes in the expression of MMP14, CAV2, and CLU post-treatment imply their role in the pathophysiology of endometriosis and may serve as a potential diagnostic biomarker of endometriosis in response to GnRHa treatment in patients with ovarian endometrioma.