Shatavarin-IV rescues the Di (2-ethylhexyl) phthalate (DEHP) induced oxidative stress in rat granulosa cells in vitro.

Studies provide notable evidence that oxidative stress (OS) mediated reactive oxygen species (ROS) disturb reproductive health. We have shown in our previous publication that exposure of Di-(2-ethylhexyl) phthalate (DEHP), induces OS mediated ROS generation which inhibits steroid synthesis. In the present study, we demonstrated the ameliorative/protective effects of one of the steroidal saponins, i.e., Shatavarin-IV, isolated from the roots of Asparagus racemosus against DEHP induced OS in rat granulosa cells. Granulosa cells were exposed with DEHP alone (400µM), Shatavarin-IV alone (8µg/ml), and a combination of DEHP + Shatavarin-IV (400µM + 8µg/ml) in vitro for 24 hrs. Intracellular ROS, OS/hypoxia, mitochondrial membrane potential, steroid-responsive genes expression were analyzed. The results revealed that the effective dose of DEHP (400µg) significantly increased OS compared to the control by increasing ROS levels, mitochondrial membrane potential, and ß-galactosidase activity with a higher level of apoptotic genes (Bax, Caspase-3) expression at mRNA level. Further, DEHP significantly (p<0.05) reduced mRNA expression of steroidogenic responsive genes (StAR, CYP17A1 and CYP19A1) in granulosa cells treated with above combination compared to control. Interestingly, co-treatment of DEHP + Shatavarin-IV significantly suppressed the DEHP induced OS, ROS, ß-galactosidase levels and enhanced steroidogeneic and apoptotic gene expression activities, which suggests that Shatavarin-IV rescued DEHP-induced changes that may useful for the prevention of DEHP- induced reproductive toxicity.

Osteonecrosis in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The relationship of inflammatory bowel disease (IBD) with osteonecrosis or avascular necrosis (AVN) is uncertain. METHODS: Systematic review to estimate the frequency of osteonecrosis in IBD was performed. Electronic databases were searched on 12 December 2022 to identify relevant studies. We planned to estimate the pooled prevalence of AVN in IBD, the risk in IBD when compared to the healthy population (without any chronic disease), and the impact of steroid use on osteonecrosis (IBD with and without steroid use). The risk of Bias was assessed with the Joanna Briggs Institute appraisal tool. RESULTS: Fifteen studies including 105 154 individuals were included. The pooled rate AVN was 10.39 per 1000 patients (95% confidence interval, 4.44-24.11, I 2  = 97%). Subgroup analysis suggested that the prevalence was lower in larger studies (>1000 participants) at 3.10, 1.07; 8.98, I 2  = 98% versus 21.03, 8.69; 50.01, I 2  = 83%. The use of steroids did not seem to increase the risk of osteonecrosis in the included studies (pooled odds ratio: 1.88, 0.55-6.41, I 2  = 39%). The systematic review was limited by the absence of comparison with the control population free of chronic disease. CONCLUSION: IBD may be associated with a risk of osteonecrosis. Future studies should assess the risk in comparison to the healthy population and the impact of disease activity and IBD therapies on the risk.

Identification and molecular characterization of genes modulating progression of an oocyte from M-I to M-II in rat ovary.

BACKGROUND: To achieve oocyte competence for successful fertilization, bidirectional communication between oocyte and granulosa cells is crucial. The acquisition of meiotic competency in oocyte is facilitated by various regulatory genes however, expression pattern of these genes is not well documented during meiotic transition from Metaphase-I to Metaphase-II stage. Therefore, the present research analyzed the expression pattern of regulatory genes that are involved in the transition from M-I to M-II stages in rat oocyte. METHODS: The analysis of the data was conducted by applying an array of bioinformatic tools. The investigation of gene group interactions was carried out by employing the STRING database, which relies on co-expression information. The gene ontology (GO) analysis was performed utilizing the comparative GO database. Functional annotation for GO and pathway enrichment analysis were performed for genes involved in networking. The GO obtained through computational simulations was subsequently validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: The findings of our study suggest that there is a distinct gene expression pattern in both the oocyte and granulosa cells. This pattern indicates that oocyte-secreted factors, such as BMP15 and GDF9, play a crucial role in regulating the progression of the meiotic cell cycle from the M-I to M-II stages. We have also examined the level of mRNA expression of genes including CYP11A1, CYP19A1, and STAR, which are crucial for the steroidogenesis. CONCLUSIONS: It is fascinating to observe that the oscillatory pattern of specific key genes may hold significance in the process of in vitro oocyte maturation, specifically during the transition from the M-I to M-II stage. It might be useful for determining biomarker genes and potential pathways that play a role in attaining oocyte competency, thereby aiding in the assessment of oocyte quality for the purpose of achieving successful fertilization.

Sarcopenia and frailty in inflammatory bowel disease: Emerging concepts and evidence.

Sarcopenia is a condition marked by progressive loss of skeletal muscle mass and function while frailty is a multidimensional concept characterized by diminished physiological reserve and increased vulnerability to stressors. Both of these were previously considered as related to aging and shown to impact the quality of life and carry prognostic significance. Emerging data show that both sarcopenia and frailty carry similar relevance in chronic illness. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and malnourishment, both of which contribute to the development of sarcopenia by increasing protein breakdown and reducing protein synthesis. The coexistence of frailty further compounds the clinical complexity of IBD patients. Published evidence suggests a bidirectional association with IBD contributing to muscle wasting, while the resultant sarcopenia and frailty could further exacerbate the disease course. Sarcopenia and frailty are independently associated with adverse outcomes, including hospitalizations, increased surgical interventions, and surgical complications. As therapeutic strategies for IBD evolve, understanding the nuanced relationship between inflammatory bowel disease, sarcopenia, and frailty is crucial for devising holistic management. Comprehensive care should encompass not only disease-modifying therapies but also interventions targeting frailty and sarcopenia, as they have been shown to have a significant impact not only on the disease course but also on the quality of life. Future research could focus on further elucidating underlying mechanisms, simple screening strategies, and developing targeted interventions to improve the overall quality of life for individuals grappling with the complex interplay of IBD, sarcopenia, and frailty.

Progression of Quantum Dots Confined Polymeric Systems for Sensorics.

The substantial fluorescence (FL) capabilities, exceptional photophysical qualities, and long-term colloidal stability of quantum dots (QDs) have aroused a lot of interest in recent years. QDs have strong and wide optical absorption, good chemical stability, quick transfer characteristics, and facile customization. Adding polymeric materials to QDs improves their effectiveness. QDs/polymer hybrids have implications in sensors, photonics, transistors, pharmaceutical transport, and other domains. There are a great number of review articles available online discussing the creation of CDs and their many uses. There are certain review papers that can be found online that describe the creation of composites as well as their many different uses. For QDs/polymer hybrids, the emission spectra were nearly equal to those of QDs, indicating that the optical characteristics of QDs were substantially preserved. They performed well as biochemical and biophysical detectors/sensors for a variety of targets because of their FL quenching efficacy. This article concludes by discussing the difficulties that still need to be overcome as well as the outlook for the future of QDs/polymer hybrids.

Analysis of the most viewed Hindi YouTube videos on breast cancer.

Background: : Breast cancer is the most common cancer diagnosed in women worldwide. Social media channels are a significant source of health information including breast cancer. YouTube has a broad range of educational materials on various health issues in many languages. However, the accuracy of these videos is contentious. This study aimed to examine the accuracy of the most viewed Hindi videos on YouTube related to breast cancer. Methods: : On YouTube, the "Breast Cancer-Hindi" term was searched for the 50 most viewed Hindi videos. To evaluate the videos' quality and reliability, global quality scores (GQS) and DISCERN (quality criteria for the assessment of written health information), and for credibility and usefulness Journal of the American Medical Association (JAMA) tool were used. Popularity was measured using a video power index (VPI). Comparisons of scores were made between professionals' and consumers' videos. Two health researchers independently rated the videos and their correlation was calculated for agreement. Results: : Of all the 50 videos viewed, 23 (46%) each were uploaded by consumers and professionals. GQS median 3 (1-5), DISCERN median 13 (5-23), JAMA median 2 (0.50-4), and VPI median 90.7 (50-96.93) were reported. All scores of professionals were higher than consumers at a significant level (P < 0.05). A significant correlation was found between both observers (P < 0.01). Conclusion: : YouTube has some good quality and reliable videos on breast cancer in the Hindi language. These videos are mostly of professionals in comparison with consumers with wide viewership. However, they are limited in numbers; therefore, health professionals should upload more videos with accurate information to spread awareness about breast cancer.

Understanding Social Media Usage and Engagement among Women to inform Breast Cancer Knowledge and Prevention Practices: Cross - sectional study in Delhi -National Capital Region of India.

BACKGROUND: Breast cancer is the major concern worldwide and in India too. Lack of awareness is one of the causes of increasing mortality rate in India. Social media is playing an important role in health communication including breast cancer information. In India, number of women are using social media. OBJECTIVE: To explore the impact of social media usage and engagement in enhancing knowledge and practices to prevent breast cancer among women of India. METHODOLOGY: A cross-sectional study was conducted in Delhi-National Capital Region of India with a sample of 649 women (response rate 83.51%). The questionnaire consisted of three sections. In first section, sociodemographic details (four items) were collected, second section contained five items on social media use and engagement and third part included items on knowledge about risk factors (seven items), symptoms (eight items), and screening (six items) of breast cancer and practice (seven items). Descriptive statistics, Chi-square, Cramer-V test, and structural equation modeling-Analysis of a moment structure were used to identify the relationship between social media engagement and knowledge and practices of women. RESULTS: Around 80% (431/542) of women have medium level of social media engagement and 20% are highly engaged. The slope coefficient of the relationship between social media engagement and knowledge is 0.805 and between knowledge and practice is 0.309, Chi-square value is 52.053 and 29.624, Cramer-V statistics is 0.310 and 0.165, respectively, which indicates significant relationship. CONCLUSION: The study result justified significant impact of social media engagement on knowledge and practices of women to prevent breast cancer.

Meiotic Instability Generates a Pathological Condition in Mammalian Ovum.

Maintenance of metaphase-II (M-II) arrest in ovum is required to present itself as a right gamete for successful fertilization in mammals. Surprisingly, instability of meiotic cell cycle results in spontaneous exit from M-II arrest, chromosomal scattering and incomplete extrusion of second polar body (PB-II) without forming pronuclei so called abortive spontaneous ovum activation (SOA). It remains unclear what causes meiotic instability in freshly ovulated ovum that results in abortive SOA. We propose the involvement of various signal molecules such as reactive oxygen species (ROS), cyclic 3',5' adenosine monophosphate (cAMP) and calcium (Ca2+) in the induction of meiotic instability and thereby abortive SOA. These signal molecules through their downstream pathways modulate phosphorylation status and activity of cyclin dependent kinase (cdk1) as well as cyclin B1 level. Changes in phosphorylation status of cdk1 and its activity, dissociation and degradation of cyclin B1 destabilize maturation promoting factor (MPF). The premature MPF destabilization and defects in other cell cycle regulators possibly cause meiotic instability in ovum soon after ovulation. The meiotic instability results in a pathological condition of abortive SOA and deteriorates ovum quality. These ova are unfit for fertilization and limit reproductive outcome in several mammalian species including human. Therefore, global attention is required to identify the underlying causes in greater details in order to address the problem of meiotic instability in ova of several mammalian species icluding human. Moreover, these activated ova may be used to create parthenogenetic embryonic stem cell lines in vitro for the use in regenerative medicine.Graphical abstract.

Cyclic nucleotide phosphodiesterase inhibitors: possible therapeutic drugs for female fertility regulation.

Cyclic nucleotide phosphodiesterases (PDEs) are group of enzymes responsible for the hydrolysis of cyclic adenosine 3', 5' monophosphate (cAMP) and cyclic guanosine 3', 5' monophosphate (cGMP) levels in wide variety of cell types. These PDEs are detected in encircling granulosa cells or in oocyte with in follicular microenvironment and responsible for the decrease of cAMP and cGMP levels in mammalian oocytes. A transient decrease of cAMP level initiates downstream pathways to cause spontaneous meiotic resumption from diplotene arrest and induces oocyte maturation. The nonspecific PDE inhibitors (caffeine, pentoxifylline, theophylline, IBMX etc.) as well as specific PDE inhibitors (cilostamide, milrinone, org 9935, cilostazol etc.) have been used to elevate cAMP level and inhibit meiotic resumption from diplotene arrest and oocyte maturation, ovulation, fertilization and pregnancy rates both in vivo as well as under in vitro culture conditions. The PDEs inhibitors are used as powerful experimental tools to demonstrate cyclic nucleotide mediated changes in ovarian functions and thereby fertility. Indeed, non-hormonal nature and reversible effects of nonspecific as well as specific PDE inhibitors hold promise for the development of novel therapeutic drugs for female fertility regulation.

Autophagy in hypoxic ovary.

Oxygen deprivation affects human health by modulating system as well as cellular physiology. Hypoxia generates reactive oxygen species (ROS), causes oxidative stress and affects female reproductive health by altering ovarian as well as oocyte physiology in mammals. Hypoxic conditions lead to several degenerative changes by inducing various cell death pathways like autophagy, apoptosis and necrosis in the follicle of mammalian ovary. The encircling somatic cell death interrupts supply of nutrients to the oocyte and nutrient deprivation may result in the generation of ROS. Increased level of ROS could induce granulosa cells as well as oocyte autophagy. Although autophagy removes damaged proteins and subcellular organelles to maintain the cell survival, irreparable damages could induce cell death within intra-follicular microenvironment. Hypoxia-induced autophagy is operated through 5' AMP activated protein kinase-mammalian target of rapamycin, endoplasmic reticulum stress/unfolded protein response and protein kinase C delta-c-junN terminal kinase 1 pathways in a wide variety of somatic cell types. Similar to somatic cells, we propose that hypoxia may induce granulosa cell as well as oocyte autophagy and it could be responsible at least in part for germ cell elimination from mammalian ovary. Hypoxia-mediated germ cell depletion may cause several reproductive impairments including early menopause in mammals.

Novel synthesis of topological insulator based nanostructures (Bi2Te3) demonstrating high performance photodetection.

The rapid progress in 2D material research has triggered the growth of various quantum nanostructures- nanosheets, nanowires, nanoribbons, nanocrystals and the exotic nature originating through 2D heterostructures has extended the synthesis of hybrid materials beyond the conventional approaches. Here we introduce simple, one step confined thin melting approach to form nanostructures of TI (topological insulator) materials, their hybrid heterostructures with other novel 2D materials and their scalable growth. The substrate and temperature dependent growth is investigated on insulating, superconducting, metallic, semiconducting and ferromagnetic materials. The temperature dependent synthesis enables the growth of single, few quintuples to nanosheets and nanocrystals. The density of nanostructure growth is seen more on fabricated patterns or textured substrates. The fabricated nanostructure based devices show the broadband photodetection from ultraviolet to near infrared and exhibit high photoresponsivity. Ultimately, this unique synthesis process will give easy access to fabricate devices on user friendly substrates, study nanostructures and scalable growth will enable their future technology applications.

Necroptosis in stressed ovary.

Stress is deeply rooted in the modern society due to limited resources and large competition to achieve the desired goal. Women are more frequently exposed to several stressors during their reproductive age that trigger generation of reactive oxygen species (ROS). Accumulation of ROS in the body causes oxidative stress (OS) and adversely affects ovarian functions. The increased OS triggers various cell death pathways in the ovary. Beside apoptosis and autophagy, OS trigger necroptosis in granulosa cell as well as in follicular oocyte. The OS could activate receptor interacting protein kinase-1(RIPK1), receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) to trigger necroptosis in mammalian ovary. The granulosa cell necroptosis may deprive follicular oocyte from nutrients, growth factors and survival factors. Under these conditions, oocyte becomes more susceptible towards OS-mediated necroptosis in the follicular oocytes. Induction of necroptosis in encircling granulosa cell and oocyte may lead to follicular atresia. Indeed, follicular atresia is one of the major events responsible for the elimination of majority of germ cells from cohort of ovary. Thus, the inhibition of necroptosis could prevent precautious germ cell depletion from ovary that may cause reproductive senescence and early menopause in several mammalian species including human.

Necrosis and necroptosis in germ cell depletion from mammalian ovary.

The maximum number of germ cells is present during the fetal life in mammals. Follicular atresia results in rapid depletion of germ cells from the cohort of the ovary. At the time of puberty, only a few hundred (<1%) germ cells are either culminated into oocytes or further get eliminated during the reproductive life. Although apoptosis plays a major role, necrosis as well as necroptosis, might also be involved in germ cell elimination from the mammalian ovary. Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise. Necroptosis is initiated by tumor necrosis factor and operated through receptor interacting protein kinase as well as mixed lineage kinase domain-like protein. The acetylcholinesterase, cytokines, starvation, and oxidative stress play important roles in necroptosis-mediated granulosa cell death. The granulosa cell necroptosis directly or indirectly induces susceptibility toward necroptotic or apoptotic cell death in oocytes. Indeed, prevention of necrosis and necroptosis pathways using their specific inhibitors could enhance growth/differentiation factor-9 expression, improve survivability as well as the meiotic competency of oocytes, and prevent decline of reproductive potential in several mammalian species and early onset of menopause in women. This study updates the information and focuses on the possible involvement of necrosis and necroptosis in germ cell depletion from the mammalian ovary.

Role of granulosa cell mitogen-activated protein kinase 3/1 in gonadotropin-mediated meiotic resumption from diplotene arrest of mammalian oocytes.

In mammals, preovulatory oocytes are encircled by several layers of granulosa cells (GCs) in follicular microenvironment. These follicular oocytes are arrested at diplotene arrest due to high level of cyclic nucleotides from encircling GCs. Pituitary gonadotropin acts at the level of encircling GCs and increases adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) and activates mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. The MAPK3/1 disrupts the gap junctions between encircling GCs and oocyte. The disruption of gap junctions interrupts the transfer of cyclic nucleotides to the oocyte that results a drop in intraoocyte cAMP level. A transient decrease in oocyte cAMP level triggers maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggers meiotic resumption from diplotene arrest in follicular oocyte. Thus, MAPK3/1 from GCs origin plays important role in gonadotropin-mediated meiotic resumption from diplotene arrest in follicular oocyte of mammals.

Impact of stress on female reproductive health disorders: Possible beneficial effects of shatavari (Asparagus racemosus).

Stress is deeply rooted in the society and women are frequently exposed to psychological, physical and physiological stressors. Psychological stress disturbs reproductive health by inducing generation of reactive oxygen species (ROS) and thereby oxidative stress (OS). The increased OS may affect physiology of ovary, oocyte quality and cause female reproductive health disorders. To overcome stress-mediated reproductive health disorders in women, shatavari (Asparagus racemosus) is frequently recommended in Ayurvedic system of medicine. Although shatavari is one of the major health tonics and most popular rasayana drugs to treat reproductive ailments of women, underlying mechanism of shatavari action at the level of ovary remains poorly understood. Based on the existing studies, we propose that shatavari may improve female reproductive health complications including hormonal imbalance, polycystic ovarian syndrome (PCOS), follicular growth and development, oocyte quality and infertility possibly by reducing OS level and increasing antioxidants level in the body. Further studies are required to elucidate the mechanism of shatavari actions at the level of ovary and oocyte that directly impacts the reproductive health of women.

Germ cell depletion from mammalian ovary: possible involvement of apoptosis and autophagy.

Mammalian ovary contains millions of germ cells during embryonic life but only few of them are culminated into oocytes that achieve meiotic competency just prior to ovulation. The majority of germ cells are depleted from ovary through several pathways. Follicular atresia is one of the major events that eliminate germ cells from ovary by engaging apoptotic as well as non-apoptotic pathways of programmed cell death. Apoptosis is characterized by several morphological changes that include cell shrinkage, nuclear condensation, membrane blebbing and cytoplasmic fragmentation by both mitochondria- as well as death receptor-mediated pathways in encircling granulosa cells and oocyte. Although necroapoptosis have been implicated in germ cell depletion, autophagy seems to play an active role in the life and death decisions of ovarian follicles. Autophagy is morphologically characterized by intracellular reorganization of membranes and increased number of autophagic vesicles that engulf bulk cytoplasm as well as organelles. Autophagy begins with the encapsulation of cytoplasmic constituents in a membrane sac known as autophagosomes. The autophagic vesicles are then destroyed by the lysosomal enzymes such as hydrolases that results in follicular atresia. It seems that apoptosis as well as autophagy could play active roles in germ cells depletion from ovary. Hence, it is important to prevent these two pathways in order to retain the germ cells in ovary of several mammalian species that are either threatened or at the verge of extinction. The involvement of apoptosis and autophagy in germ cell depletion from mammalian ovary is reviewed and possible pathways have been proposed.

Journey of oocyte from metaphase-I to metaphase-II stage in mammals.

In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes maturation promoting factor (MPF) and induces meiotic resumption. Several signal molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation. Rho family GTPase is another enzyme that along with cell division cycle (Cdc42) to form actomyosin contractile ring required for chromosomal segregation. In the presence of origin recognition complex (ORC4), eccentrically localized haploid set of chromosomes trigger cortex differentiation and determine the division site for polar body formation. The actomyosin contractile activity at the site of division plane helps to form cytokinetic furrow that results in the formation and extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated by several factors and pathways that enable oocyte to extrude PB-I. Quality of oocyte directly impact fertilization rate, early embryonic development, and reproductive outcome in mammals.