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Following its benchmark discovery, nitric oxide (NO) is now known to play important functional roles in a variety of physiological systems. Within the vasculature, NO induces vasodilation, inhibits platelet aggregation, prevents neutrophil/platelet adhesion to endothelial cells, inhibits smooth muscle cell proliferation and migration, regulates programmed cell death (apoptosis) and maintains endothelial cell barrier function. NO generated by neurons acts as a neurotransmitter, whereas NO generated by macrophages in response to invading microbes acts as an antimicrobial agent. Because neurons, blood vessels and cells of the immune system are integral parts of the reproductive organs, and in view of the important functional role that NO plays in those systems, it is likely that NO is an important regulator of the biology and physiology of the reproductive system. Indeed, in the past 10 years, NO has established itself as a polyvalent molecule which plays a decisive role in regulating multiple functions within the female as well as the male reproductive system. This review provides an overview of the role of NO in various reproductive organs under physiological and pathological conditions. [ABSTRACT FROM PUBLISHER]

Investigates whether cultured bovine oviduct epithelial cells and fibroblasts synthesize leukemia inhibitory factor (LIF). Measurement of the LIF production in the conditioned medium of oviduct epithelial cells and fibroblasts using LIF enzyme-linked immunosorbent assay; LIF reverse transcriptase-polymerase chain reaction in extracts of RNA from oviduct epithelial/fibroblast cells.

Background: Maple Syrup Urine Disease (MSUD) is a rare inherited disorder of metabolism, which manifests early in life in classical forms. Recurrent illness and exertion aggravate neurotoxicity. This case highlights MSUD diagnosed in association with COVID-19 complications from Nepal., Case Presentation: We present a case of a 4-month-old child with a biochemical diagnosis of flared-up MSUD. Initially presenting with chief complaints of fever, noisy breathing, chest retraction, cough along with lethargy and poor feeding since the first week of life, the child also had developmental delay with feeble neck holding and absent social smile. The child was diagnosed with COVID-19 pneumonia and admitted in the Intensive Care Unit, requiring mechanical ventilation for 12 days. Despite the clinical resolution of pneumonia, the child had multiple episodes of generalized seizures and was sickly and frail. An incessant peculiar odor emanating from the child led to strong suspicion of metabolic disorder. Qualitative screening for amino acids (FeCl 3 and 2,4-dinitrophenylhdrazine/DNPH) in urine and further gas chromatography-mass spectrometry revealed increased branched-chain amino acids(valine, leucine, and isoleucine). With dietary restrictions, the child was doing well. However, unfortunately, after 10 days of discharge, the child succumbed to death., Conclusions: This case highlights the outpouring of hidden metabolic disorders with the onset of new diseases. It could have been detected and managed earlier with expedited neonatal screening and proper intervention., Competing Interests: Declarations. Ethics approval and consent to participate: This study aligns with the principles of Helinski’s declarations. The child’s guardian provided written as well as verbal consent for their inclusion and publication purpose which can be made available to the editor. Consent for publication: Written informed consent for publication was obtained from the child’s guardians. All laboratory and pathologic findings and images are anonymized and no patient identification is reported. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Pericytes (PCs) contribute to brain capillary/BBB integrity and PC migration is a hallmark for brain capillary leakage following pro-inflammatory insults. Estradiol promotes endothelial barrier integrity by inhibiting tumor necrosis factor-alpha (TNF-α)-induced PC migration. However, the underlying mechanisms remain unclear. Since micro-RNAs (miRs) regulate BBB integrity and increases in miR638 and TNF-α occur in pathological events associated with capillary leakage, we hypothesize that TNF-α mediates its capillary disruptive actions via miR638 and that estradiol blocks these actions. Using quantitative reverse transcription PCR, we first assessed the modulatory effects of TNF-α on miR638. The treatment of PCs with TNF-α significantly induced miR638. Moreover, transfection with miR638 mimic induced PC migration, whereas inhibitory miR638 (anti-miR) abrogated the pro-migratory actions of TNF-α, suggesting that TNF-α stimulates PC migration via miR638. At a molecular level, the pro-migratory effects of miR638 involved the phosphorylation of ERK1/2 but not Akt. Interestingly, estradiol downregulated the constitutive and TNF-α-stimulated expression of miR638 and inhibited the TNF-α-induced migration of PCs. In PCs treated with estrogen receptor (ER) ER-α, ER-β, and GPR30 agonists, a significant downregulation in miR638 expression was solely observed in response to DPN, an ER-β agonist. DPN inhibited the pro-migratory effects of TNF-α but not miR638. Additionally, the ectopic expression of miR638 prevented the inhibitory effects of DPN on TNF-α-induced PC migration, suggesting that interference in miR638 formation plays a key role in mediating the inhibitory actions of estradiol/DPN. In conclusion, these findings provide the first evidence that estradiol inhibits TNF-α-induced PC migration by specifically downregulating miR638 via ER-β and may protect the neurovascular unit during injury/stroke via this mechanism.

Whilst energetic and kinetic aspects of folding processes are meanwhile well understood for natural biomacromolecules, the folding dynamics in so far studied artificial foldamer counterparts remain largely unexplored. This is due to the low energy barriers between their conformational isomers that make the dynamic processes undetectable with conventional methods such as UV/Vis absorption, fluorescence, and NMR spectroscopy, making such processes 'invisible'. Here we present an asymmetric perylene bisimide dimer (bis-PBI 1) that possesses conformational chirality in its folded state. Owing to the large interconversion barrier (≥116 kJ mol -1 ), four stereoisomers could be separated and isolated. Since the interconversion between these stereoisomers requires the foldamer to first open and then to re-fold, the transformation of one stereoisomer into others allowed us to 'visualize' the dynamics of folding with time and determine its lifetimes and the energetic barriers associated with the folding process. Supported by quantum chemical calculations, we identified the open structure to be only a fleetingly metastable state of higher energy. Our experimental observation of the kinetics associated with the molecular dynamics in the PBI foldamer advances the fundamental understanding of folding in synthetic foldamers and paves the way for the design of smart functional materials., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: The purpose of this study was to investigate the association of subclinical hypothyroidism with High sensitive C-reactive protein and lipid profile which can predispose to development of Cardiovascular disease., Methods: This hospital-based comparative cross-sectional study was conducted for a period of six months. A total of 71 patients with subclinical hypothyroidism and 37 healthy control subjects were enrolled for the study. Thyroid hormones, lipid profile, hs- CRP were measured and lipid variables were used to calculate lipid indices. Student t-test were used to compare means and Spearmans correlation was done to determine the association between variables. ROC curve analysis was used to determine the diagnostic value of tests., Results: Out of 71 cases and 37 control, majority had female preponderance (71.8% in case and 83.8% in control). The mean values between case and control groups for High sensitive C-Reactive Protein, Atherogenic index of plasma, Lipoprotein combined index and non-High Density Lipoprotein cholesterol were statistically significant. There was positive correlation between Thyroid Stimulating Hormone and High sensitive C-Reactive Protein r=0.492, p 0.001, Atherogenic index of plasma and Thyroid Stimulating Hormone r=0.430, p 0.001, Lipoprotein combined index and Thyroid Stimulating Hormone (r=0.269, p =0.005), Thyroid Stimulating Hormone and non-High Density Lipoprotein cholesterol (r=0.308, p=0.001) and Atherogenic Index and Low Density Lipoprotein r= 0.712, p 0.001 with weak correlation with statistical significance as per Spearmans correlation. Area under ROC curve for High sensitive C-Reactive Protein indicated it as a positive biomarker for cardiovascular risk assessment., Conclusions: Our findings shows that sch patients are more at risk of cvd and hs-crp contributes as a significant marker, thus requiring timely intervention. Lipid indices and AIP must be determined even in patients with a normal lipid profile to improve atherogenic risk.

The encapsulation of more than one guest molecule into a synthetic cavity is a highly desirable yet a highly challenging task to achieve for neutral supramolecular hosts in organic media. Herein, we report a neutral perylene bisimide cyclophane, which has a tailored chiral cavity with an interchromophoric distance of 11.2 Å, capable of binding two aromatic guests in a π-stacked fashion. Detailed host-guest binding studies with a series of aromatic guests revealed that the encapsulation of the second guest in this cyclophane is notably more favored than the first one. Accordingly, for the encapsulation of the coronene dimer, a cooperativity factor (α) as high as 485 was observed, which is remarkably high for neutral host-guest systems. Furthermore, a successful chirality transfer, from the chiral host to encapsulated coronenes, resulted in a chiral charge-transfer (CT) complex and the rare observation of circularly polarized emission originating from the CT state for a noncovalent donor-acceptor assembly in solution. The involvement of the CT state also afforded an enhancement in the luminescence dissymmetry factor ( g lum ) value due to its relatively large magnetic transition dipole moment. The 1:2 binding pattern and chirality-transfer were unambiguously verified by single-crystal X-ray diffraction analysis of the host-guest superstructures.

Sickle cell disease (SCD)-associated chronic hemolysis promotes oxidative stress, inflammation, and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell-free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD-related hepatobiliary injury have not been fully elucidated yet. Here we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane-bound CD163. Hemolysis and increase in hepatic heme, hemoglobin, and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that heme oxygenase-1 (HO-1) positively regulates membrane-bound CD163 expression independent of nuclear factor erythroid 2-related factor 2 (NRF2) signaling in SCD liver. We further demonstrate that the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD-associated hepatobiliary injury. Understanding the role of HO-1 in membrane-bound CD163 regulation may help identify novel therapeutic targets for hemolysis-induced chronic liver injury.

An iterative step-by-step synthetic approach is employed to form perylene bisimide (PBI) oligomers of defined sizes by connecting the PBI units through their imide positions via a benzyl linker. The versatility of this approach was showcased by its successful implementation on two different PBI building blocks to achieve two separate series of oligomers (up to the pentamer) with modulated conformations: one with an open random coil oligomer and one with an H-type foldamer architecture.

The abnormal growth of oligodendrocyte precursor cells (OPCs) significantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-Methoxyestradiol (2ME), an endogenous tubulin-interacting metabolite of estradiol, is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions, it is undergoing phase II clinical trials. We hypothesize that 2ME may prevent glioma growth by targeting OPC growth. Here, we tested this hypothesis by assessing the impact of 2ME on the growth of an OPC line, "Oli-neu", and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentration-dependent manner, accompanied by significant upregulation in the expression of p21 and p27, which are negative cell-cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater, 2ME induced apoptosis, with increased expressions of caspase 3, PARP, and caspase-7 fragments, externalized phosphatidylserine staining/APOPercentage, and increased mitochondrial activity. Flow cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2, and p53 expression, as well as OPC fusion, which are key mechanisms driving endoreduplication and whole-genome duplication. Importantly, the inhibition of p53 with pifithrin-α rescued 2ME-induced endoreduplication. The pro-apoptotic and endoreduplication actions of 2ME were accompanied by the upregulation of survivin, cyclin A, Cyclin B, Cyclin D2, and ppRB. Similar growth inhibitory, apoptotic, and endoreduplication effects of 2ME were observed in CG4 cells. Taken together, our findings provide evidence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs into survival (fight or flight) mode, leading to endoreduplication. This inherent survival characteristic of OPCs may, in part, be responsible for drug resistance in gliomas, as observed for many tubulin-interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on the cell-cycle status of individual cells. Combining tubulin-interfering molecules with drugs such as pifithrin-α that inhibit endoreduplication may help inhibit OPC/glioma growth and limit drug resistance.

Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African-Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive liver injury in SCD. Liver-resident macrophages and monocytes are known to enable the clearance of HbS; however, the role of liver sinusoidal endothelial cells (LSEC) in HbS clearance and liver injury in SCD remains unknown. Using real-time intravital (in vivo) imaging in mice liver as well as flow cytometric analysis and confocal imaging of primary human LSEC, we show for the first time that liver injury in SCD is associated with accumulation of HbS and iron in the LSEC, leading to senescence of these cells. Hemoglobin uptake by LSEC was mediated by micropinocytosis. Hepatic monocytes were observed to attenuate LSEC senescence by accelerating HbS clearance in the liver of SCD mice; however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver. These findings are the first to suggest that LSEC contribute to HbS clearance and HbS-induced LSEC senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis-induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC-mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD.

Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs' proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells' ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs' functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells' secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes.

Background: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia., Case Presentation: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 μmol/L), and serum uric acid (560 μmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst., Conclusions: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus., (© 2024. The Author(s).)

Introduction: Polycystic ovary syndrome is a common hormonal disorder that affects women of reproductive age which is characterized by hyperandrogenism, polycystic ovarian morphology, ovarian dysfunction, and hyperinsulinemia. Increased prevalence of cardiovascular disease and higher cardiovascular morbidity is seen in women with polycystic ovary syndrome. This study aimed to estimate the prevalence of high serum homocysteine levels among women with polycystic ovarian syndrome visiting an infertility clinic of a tertiary care centre., Methods: This was a descriptive cross-sectional study conducted among women with polycystic ovarian syndrome visiting an infertility clinic at the Department of Obstetrics and Gynaecology of a tertiary care centre from 1 June 2023 to 1 September 2023. The study was conducted after obtaining ethical approval from the Institutional Review Committee. Biochemical analysis of gonadal hormones, serum homocysteine and lipid profile was done. A convenience sampling method was used. The point estimate was calculated at a 95% confidence interval., Results: Among 76 women, the prevalence of high serum homocysteine level was found in 54 (71.05%) (60.86-81.25, 95% Confidence Interval). The mean age of patients was 27.46±6.18 years., Conclusions: The prevalence of high homocysteine levels among women with polycystic ovarian syndrome is higher than other studies done in similar settings., Keywords: body mass index; homocysteine; polycystic ovary syndrome; prevalence.

Vitamin D deficiency is a global public health concern that provokes bone demineralization and weakening. In response to the decreased vitamin D level, calcium stores wear out. The homeostatic effect of compensatory hyperparathyroidism in vitamin D deficiency incites variable discrepancies in different populations. This study intends to decipher the transition point of PTH in relation to levels of vitamin D in a Nepalese population. A cross-sectional study was carried out at Tribhuvan University Teaching Hospital, Nepal. Serum calcium, phosphorus, intact PTH, and 25-hydroxy vitamin D levels were assayed in an Abbott ARCHITECT Integrated System. A correlation plot of PTH and vitamin D was analyzed in Statistical Package for Social Sciences version 22.0. Using a locally weighted scatter plot smoothing method, the relation between these variables was presented graphically. Among 281 individuals, 30.2% had vitamin D levels below 20 ng/mL. There was an archetypical transition in the PTH levels in concert with the decrease in vitamin D level marked by 2 inflection points (ie, 18.5 and 42.0 ng/mL). Our findings suggest that to augment overall health and avert weakness due to vitamin D deficiency, the levels of vitamin D should be maintained above 42.0 ng/mL in our population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Tecoma stans is a widely distributed tall ornamental shrub in the plains of Indian subcontinent and is considered an invasive species across Argentina, Australia, South Africa, Pacific Islands and tropical regions of Asia. Besides having an ornamental significance, T. stans has been extensively investigated for its pharmaceutical applications as a source of bioactive compounds. In addition, the shrub is cultivated commercially as a potted flowering plant. We believe that T. stans, being a hardy, invasive and aggressively growing species, holds a considerable potential and a promising solution for re-greening waste and degraded lands outside its invasive range, due to its wider adaptability and drought tolerant characteristics. The shrub is an excellent source of pollen and nectar, that attracts diverse insect-pollinators and several species of birds. The prudent plantation of this shrub has the potential to restore the ecology of barren landscapes, that can change its perspective of 'being invasive' to 'being ecologically healthy' across the tropical, semi-arid and subtropical regions worldwide. This paper reviews the current updates on ecology, life cycle including morphology, plant growth characteristics, flowering phenology, reproductive biology, breeding system and fruiting of T. stans. In addition, details on insect-pollinator diversity and natural regeneration potential have also been discussed, besides highlighting its therapeutic and landscape use., (© 2024. The Author(s).)

Cigarette smoking is associated with a higher risk of ICU admissions among patients with flu. However, the etiological mechanism by which cigarette smoke (CS) exacerbates flu remains poorly understood. Here, we show that a mild dose of influenza A virus promotes a severe lung injury in mice preexposed to CS but not room air for 4 weeks. Real-time intravital (in vivo) lung imaging revealed that the development of acute severe respiratory dysfunction in CS- and flu-exposed mice was associated with the accumulation of platelet-rich neutrophil-platelet aggregates (NPAs) in the lung microcirculation within 2 days following flu infection. These platelet-rich NPAs formed in situ and grew larger over time to occlude the lung microvasculature, leading to the development of pulmonary ischemia followed by the infiltration of NPAs and vascular leakage into the alveolar air space. These findings suggest, for the first time to our knowledge, that an acute onset of platelet-driven thrombo-inflammatory response in the lung contributes to the development of CS-induced severe flu.

Terrestrial and aquatic ecosystems have specific carbon fingerprints and sequestration potential, due to the intrinsic properties of the organic matter (OM), mineral content, environmental conditions, and microbial community composition and functions. A small variation in the OM pool can imbalance the carbon dynamics that ultimately affect the climate and functionality of each ecosystem, at regional and global scales. Here, we review the factors that continuously contribute to carbon stability and lability, with particular attention to the OM formation and nature, as well as the microbial activities that drive OM aggregation, degradation and eventually greenhouse gas emissions. We identified that in both aquatic and terrestrial ecosystems, microbial attributes (i.e., carbon metabolism, carbon use efficiency, necromass, enzymatic activities) play a pivotal role in transforming the carbon stock and yet they are far from being completely characterised and not often included in carbon estimations. Therefore, future research must focus on the integration of microbial components into carbon mapping and models, as well as on translating molecular-scaled studies into practical approaches. These strategies will improve carbon management and restoration across ecosystems and contribute to overcome current climate challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Silver nanoparticles (AgNPs) have garnered significant attention in recent years due to their unique properties and diverse applications across various industries. This review provides an overview of the synthesis methods, characterization techniques, applications, regulatory guidelines, and challenges associated with AgNPs. Green synthesis routes, utilizing natural extracts or biomolecules, have emerged as environmentally sustainable alternatives for producing AgNPs with reduced environmental impact. Characterization techniques such as spectroscopy, microscopy, and chromatography are employed to analyze the physicochemical properties of AgNPs and ensure their quality and stability. AgNPs find applications in biomedical, environmental, and consumer product sectors, including wound dressings, water purification filters, cosmetics, and medical devices, owing to their antimicrobial, catalytic, and optical properties. Regulatory guidelines play a crucial role in ensuring the safe and responsible use of AgNPs, addressing concerns related to biocompatibility, toxicity, and environmental impact. However, challenges remain in standardization, scalability, and long-term safety assessment of AgNP-based products. Future research efforts should focus on optimizing synthesis methods, enhancing characterization techniques, and addressing regulatory gaps to unlock the full potential of AgNPs while ensuring their safety and sustainability. Overall, AgNPs offer promising opportunities for addressing global challenges and driving technological innovation across diverse sectors.

Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, presents a complex and challenging clinical scenario characterized by chronic inflammation of the gastrointestinal tract. Traditional herbal medicine has garnered increasing interest as a potential adjunctive or alternative therapy for IBD, owing to its perceived efficacy, safety profile, and holistic approach to health. This review provides a comprehensive overview of the current landscape of herbal interventions for IBD, addressing scientific, regulatory, clinical, and patient-related considerations. Scientifically, the exploration of herbal interventions faces challenges related to the complexity of herbal formulations, standardization, and quality control. Regulatory hurdles encompass stringent requirements for safety, efficacy, and quality standards, necessitating adherence to robust preclinical and clinical protocols. Clinically, the heterogeneity of the patient population, potential interactions with conventional therapies, and patient preferences pose challenges in the integration of herbal interventions into clinical practice.

Madagascar periwinkle (Catharanthus roseus) is a plant species known for its rich pharmacological and phytochemical properties. This systematic review aims to comprehensively evaluate the potential of Madagascar periwinkle as a dietary supplement. A thorough search of relevant databases yielded studies focusing on the pharmacological activities and phytochemical constituents of Madagascar periwinkle. The review highlights the diverse pharmacological effects of Madagascar periwinkle, including anti-cancer, anti-diabetic, anti-inflammatory, and antimicrobial properties, among others. Furthermore, the phytochemical analysis revealed the presence of various bioactive compounds such as alkaloids, flavonoids, terpenoids, and phenolics, which contribute to its medicinal properties. Despite the promising findings, further research is warranted to elucidate the mechanisms of action, safety profile, and potential interactions of Madagascar periwinkle as a dietary supplement. Overall, this systematic review provides valuable insights into the pharmacological and phytochemical profiles of Madagascar periwinkle, suggesting its potential as a natural dietary supplement with diverse health benefits.

Introduction: Polycystic ovarian syndrome is the most common endocrine-metabolic disorder, affecting women of reproductive age groups, which shares various symptoms with thyroid dysfunctions. Despite it predisposition of aforesaid cohorts to autoimmunity, these etiologies have not adequately been studied in them. This study aimed to find out the prevalence of positive thyroid peroxidase antibodies among women with polycystic ovarian syndrome visiting an infertility clinic at a tertiary care centre., Methods: This was a cross-sectional study conducted at a tertiary care centre among patients visiting the infertility clinic at the Department of Obstetrics and Gynaecology from 21 September 2022 to 21 February 2023. Biochemical analysis of thyroid hormones, gonadal hormones, anti-mullerian hormone and thyroid peroxidase antibody were done in Abbott ARCHITECT ci4100 and SNIBE Maglumi 800 autoanalyzer. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Among 70 participants, thyroid peroxidase antibody was positive in 16 (22.86%) (13.02-32.69, 95% Confidence Interval). The mean age of the patients was 28.25±5.26 years. In the individuals with thyroid-stimulating hormone below 2.5 mIU/l, 5 (31.25%) had positive thyroid peroxidase antibody titre., Conclusions: The prevalence of positive thyroid peroxidase antibodies among women with polycystic ovarian syndrome is similar to other studies done in similar settings. Regular monitoring of thyroid peroxidase antibodies is recommended in these women to guide conception in order to evade inevitable adverse pregnancy outcomes., Keywords: anti-thyroid autoantibodies; autoimmunity; infertility; prevalence; polycystic ovary syndrome.

Background: Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles., Methods: This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables., Results: Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal., Conclusion: The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion, and sterile inflammation. The administration of oral L-glutamine has been shown to reduce the frequency of pain in SCD patients; however, the long-term effect of L-glutamine in SCD remains to be determined. To understand the long-term effect of L-glutamine administration in the liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic L-glutamine administration reduces hepatic hemoglobin-heme-iron levels but fails to ameliorate ischemic liver injury. Remarkably, we found that this failure in the resolution of hepatobiliary injury and persistent liver fibrosis is associated with the reduced expression of hepatic Kupffer cells post-L-glutamine treatment. These findings establish the importance of investigating the long-term effects of L-glutamine therapy on liver pathophysiology in SCD patients.

Human path-planning operates differently from deterministic AI-based path-planning algorithms due to the decay and distortion in a human's spatial memory and the lack of complete scene knowledge. Here, we present a cognitive model of path-planning that simulates human-like learning of unfamiliar environments, supports systematic degradation in spatial memory, and distorts spatial recall during path-planning. We propose a Dynamic Hierarchical Cognitive Graph (DHCG) representation to encode the environment structure by incorporating two critical spatial memory biases during exploration: categorical adjustment and sequence order effect. We then extend the "Fine-To-Coarse" (FTC), the most prevalent path-planning heuristic, to incorporate spatial uncertainty during recall through the DHCG. We conducted a lab-based Virtual Reality (VR) experiment to validate the proposed cognitive path-planning model and made three observations: (1) a statistically significant impact of sequence order effect on participants' route-choices, (2) approximately three hierarchical levels in the DHCG according to participants' recall data, and (3) similar trajectories and significantly similar wayfinding performances between participants and simulated cognitive agents on identical path-planning tasks. Furthermore, we performed two detailed simulation experiments with different FTC variants on a Manhattan-style grid. Experimental results demonstrate that the proposed cognitive path-planning model successfully produces human-like paths and can capture human wayfinding's complex and dynamic nature, which traditional AI-based path-planning algorithms cannot capture.

Understanding the interplay between the kinetics and energetics of photophysical processes in perovskite-chromophore hybrid systems is crucial for realizing their potential in optoelectronics, photocatalysis, and light-harvesting applications. By combining steady-state optical characterizations and transient absorption spectroscopy, we have investigated the mechanism of interfacial charge transfer (CT) between colloidal CsPbBr 3 nanoplatelets (NPLs) and surface-anchored perylene derivatives and have explored the possibility of controlling the CT rate by tuning the driving force. The CT driving force was tuned systematically by attaching acceptors with different electron affinities and by varying the bandgap of NPLs via thickness-controlled quantum confinement. Our data show that the charge-separated state is formed by selectively exciting either the electron donors or acceptors in the same system. Upon exciting attached acceptors, hole transfer from perylene derivatives to CsPbBr 3 NPLs takes place on a picosecond time scale, showing an energetic behavior in line with the Marcus normal regime. Interestingly, such energetic behavior is absent upon exciting the electron donor, suggesting that the dominant CT mechanism is energy transfer followed by ultrafast hole transfer. Our findings not only elucidate the photophysics of perovskite-molecule systems but also provide guidelines for tailoring such hybrid systems for specific applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objectives: This study intends to determine the association of parathormone with vitamin D and other biochemical parameters (calcium and phosphate) and evaluate the relationship between low vitamin D and parathormone levels., Methods: A hospital-based cross-sectional study was conducted among 310 study participants over the period of 1 year. Patients who underwent laboratory investigations for vitamin D, parathormone, calcium, and phosphate in the Clinical Biochemistry Laboratory at the Institute of Medicine, Tribhuvan University Teaching Hospital were included. Serum intact parathyroid hormone, vitamin D, calcium, and phosphate were measured in Abbott Architect (ci4100) integrated system autoanalyzer., Results: Among the 310 study participants, 177 (57%) were males and 43% were females. The mean age of the patient was 47.09 ± 19.01 years. High intact parathyroid hormone (>68 pg/ml) was observed in 73% of the patients. Low vitamin D (<20 ng/ml) was present in 30.2% of the patients. The findings from our study depict that there is a negative significant correlation between intact parathyroid hormone levels, vitamin D, and calcium levels and a positive correlation between intact parathyroid hormone and phosphate levels ( p  < 0.001)., Conclusions: The findings from our study illustrate that there is a swapping drift in the profile of hyperparathyroidism in the Nepalese population. We report the presence of hyperparathyroidism in the middle age group than in the older age group contradictory to that reported in the literature., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrinopathy in women of reproductive age group and is highly associated with an increased risk of diabetes, hypertension, cardiovascular disease, and hyper estrogen-related malignancies in women with PCOS. This study was intended to assess the metabolic and hormonal profile of the patients with polycystic ovarian syndrome attending a tertiary care hospital., Methodology: A descriptive cross-sectional study was conducted among 107 women diagnosed with polycystic ovarian syndrome from the Department of Clinical Biochemistry of Tribhuvan University and Teaching Hospital. Descriptive analysis was performed to determine the socio-demographic characteristics of the participants. Bivariate analysis was conducted to determine using a t-test for comparing means between two groups and ANOVA for comparing the hormonal and metabolic parameters., Results: The mean age of the participants was 27 ± 4 years. This study showed that blood pressure was significantly higher in overweight and obese women (p = 0.001). The obese group had significantly higher serum TSH than the normal group (10.04 vs. 2.73, p = 0.001). Abnormal glucose and hyperinsulinemia were present in 4% of the patients, while 40% had Vitamin D deficiency. Hypothyroidism (TSH ≥ 4.5 mIU/ml) was found in 11% of the PCOS participants with a mean value of 6.65 ± 21.17 mIU/ml. Hyperprolactinemia ≥ 26.8 ng/ml was depicted in 21% of the study population with a mean value of 37.25 ± 21.86 ng/ml., Conclusion: Our study demonstrated that PCOS is most commonly prevalent in young women of the reproductive age group which can lead to reproductive, metabolic, and oncological complications in the long term. LH/ FSH ratio was found to be significantly deranged indicating that PCOS should be diagnosed and treated early in the adolescent age group., (© 2023. The Author(s).)

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)/lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC + MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC + MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK1/2 and Akt phosphorylation in LECs and LEC + MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC + MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK1/2 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC + MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukin/cytokine-mediated signaling, innate immune system, ERK1/2 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA1/2, IFITM1, HLA-A/B, PSMB8/9, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer.