Monogenic Diabetes: A Comprehensive Overview and Therapeutic Management of Subtypes of Mody.

BACKGROUND: Monogenic diabetes often occurs as a result of single-gene mutations. The illness is minimally affected by environmental and behavioral factors, and it constitutes around one to five percent of all cases of diabetes. METHODS: Newborn diabetes mellitus (NDM) and maturity-onset diabetes of the young (MODY) are the predominant causes of monogenic diabetes, accounting for a larger proportion of cases, while syndromic diabetes represents a smaller percentage. MODY, a group of inherited non-autoimmune diabetes mellitus disorders, is quite common. However, it remains frequently misdiagnosed despite increasing public awareness. The condition is characterized by insulin resistance, the development of diabetes at a young age (before 25 years), mild high blood sugar levels, inheritance in an autosomal dominant pattern, and the preservation of natural insulin production. RESULTS: Currently, there are 14 distinct subtypes of MODY that have been identified. Each subtype possesses distinct characteristics in terms of their frequency, clinical symptoms, severity of diabetes, related complications, and response to medicinal interventions. Due to the clinical similarities, lack of awareness, and high expense of genetic testing, distinguishing between type I (T1D) and type II diabetes mellitus (T2D) can be challenging, resulting in misdiagnosis of this type of diabetes. As a consequence, a significant number of individuals are being deprived of adequate medical attention. Accurate diagnosis enables the utilization of novel therapeutic strategies and enhances the management of therapy in comparison to type II and type I diabetes. CONCLUSION: This article offers a concise overview of the clinical subtypes and characteristics of monogenic diabetes. Furthermore, this article discusses the various subtypes of MODY, as well as the process of diagnosing, managing, and treating the condition. It also addresses the difficulties encountered in detecting and treating MODY.

Differential Gene Expression Analysis of Human Ovarian Follicular Cumulus and Mural Granulosa Cells Under the Influence of Insulin in IVF Ovulatory Women and Polycystic Ovary Syndrome Patients Through Network Analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a commonly occurring reproductive disorder among the reproductive-aged women. Its global occurrence varies based on diagnostic guidelines, ethnicities, and locations of concern. Insulin resistance (IR) is commonly observed around 65-70% of women diagnosed with PCOS, representing a prevalent association. Consequently, the study was designed with an objective of illustrating the effect of insulin on mural and cumulus granulosa cells (GCs) of PCOS patients in comparison to normal ovulating women. METHODOLOGY: This study is a case-control design, wherein a total of 80 participants were recruited meeting criterion of inclusion and exclusion, divided into 8 groups with each group consisting of 10 samples. The process involves the isolation and culturing of mural granulosa cells (MGC) and cumulus granulosa cells (CGC) with and without exposure to insulin. The proteins released by untreated GCs and insulin-treated GCs were extracted, and complex protein mixtures were digested with trypsin, followed by tandem mass spectrometry analysis and data processing using bioinformatics. RESULTS: We found 595 proteins in both control and PCOS samples, of which 310 were contributed by MGCs and 285 by CGCs. The PCOS MGCs expressed 20%, both the normal MGCs and CGCs have equal representation of 16% by each, whereas the PCOS CGCs proteins contributed 15% of the total of the proteomic expression. However, the poor expression observed with the Insulin exposure, the Insulin treated PCOS CGCs contributes 13%, PCOS MGCs contributes 8%. The normal MGCs upon the Insulin treatment give 8% then and there only 4% of proteins expressed by normal CGCs after Insulin treatment. The Venn analysis widened on their precise expression topographies. The examination of strings exhibited important protein-protein interaction pathways. CONCLUSION: This is a pioneering investigation aimed to establish the link between hyperinsulinemia in localized follicular GCs and PCOS mechanisms by comparing them to control group. The examination of various attributes, mechanisms, and traits shown by genes and proteins in individuals with PCOS compared to control populations, alongside the investigation of the dynamics of these genes and proteins following exposure to insulin, holds promise for the formulation of novel hypotheses and strategies in the identification of new biomarkers.

Phytochemistry and Therapeutic Potential of Cupressus torulosa Needles Essential Oil from India.

Cupressus torulosa is an evergreen tree with a wide distribution in north-western Himalayan region of India. Its needles have long been used in traditional medicine for anti-inflammatory, antimicrobial, and wound-healing properties. This study aimed to scientifically validate the traditional claim of the needles to treat inflammation by evaluating the chemical composition, antioxidant potential, and anti-inflammatory activity of the essential oil extracted from the needles (CTEO) using hydro-distillation. Qualitative and quantitative chemical composition of the CTEO was determined with the aid of GC-MS and GC-FID techniques. The major constituents of the CTEO were terpinen-4-ol (393.8±12.5 µg/mg), totarol (55.0±17.2 µg/mg), and sabinene (43.7±2.8 µg/mg). CTEO exhibited significant antioxidant activity when evaluated using DPPH free radical scavenging and reducing power assays. Furthermore, the CTEO demonstrated good anti-inflammatory behavior in in vitro egg albumin denaturation assay, with an IC50 of 27.32 µg/mL. In vivo tests using carrageenan-induced paw edema and xylene-induced ear edema in rats showed significant effects at doses of 30 mg/kg for up to 1 hour. The significant discoveries not only support the established assertions about the anti-inflammatory properties of C. torulosa needles but also highlight their potential as a useful resource in the growing herbal, complementary, and alternative medicine sectors.

A review on recent advancements in pharmaceutical technology transfer of tablets from an Indian perspective.

OBJECTIVE: The healthcare sector is a paramount and rapidly expanding industry in India. The pharmaceutical field in India has experienced substantial growth and transformation in recent times, making significant contributions to the global healthcare market. This comprehensive review delves into the most recent innovations in pharmaceutical technology transfer (TT), particularly in the context of tablet formulations from an Indian standpoint. SIGNIFICANCE: The pharmaceutical sector has grappled with various challenging issues, including the escalating costs of medications and the demand for patient-friendly products. METHODS: In this technological progress era, various cutting-edge pharmaceutical technologies, such as artificial intelligence (AI), and 3D and 4D printing, play pivotal roles in drug development. Tablets, the most promising and widely utilized dosage form worldwide, require a sophisticated approach to TT. Achieving a successful TT necessitates a dedicated team with well-defined objectives, improved documentation, and effective communication. RESULTS: The Indian Pharmaceutical Industry (IPI) possesses the potential to make significant contributions to the global healthcare sector. Moreover, we delve into the various phases of TT, highlighting the pivotal role of formulation development and process optimization in ensuring product quality, efficiency, and cost-effectiveness along with different models of TT. Additionally, we examine the challenges associated with TT and potential solutions, as well as the initiatives of the Indian government to bolster the Indian pharmaceutical sector's position as the "Pharmacy of the World". CONCLUSION: It is concluded that there is a need to contextualize and institutionalize the tech transfer policies for successful implementation for the benefit of the global population.

Graphene quantum dot doped viscoelastic lyotropic liquid crystal nanocolloids for antibacterial applications.

Graphene quantum dots (GQDs) are prepared and characterized via X-ray diffraction (XRD), UV-Visible spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and photoluminescence (PL). GQDs are doped (5 mg and 10 mg) in the lyotropic liquid crystalline (LLC) lamellar and hexagonal phases to prepare GQD/LLC nanocolloids. Polarizing optical microscopy and X-ray diffraction measurement reveals that GQDs do not affect the lamellar and hexagonal LLC structures and may organize on their interface. Pure LLC phases and nanocolloids are studied for steady and dynamic rheological behavior. LLC phases and GQD/LLC nanocolloids possess shear thinning and frequency dependent liquid viscoelastic behavior. A complex moduli study of LLCs and GQD/LLC nanocolloids is carried out which indicates the gel to viscous transition in LLCs and GQD/LLC nanocolloids as a function of frequency. LLC phases and GQD/LLC nanocolloids are tested for antibacterial activity against Listeria ivanovii. The effect of surfactant concentration, LLC phase geometry and GQD concentration has been studied and discussed. A probable mechanism for the strong antimicrobial activity of LLCs and GQD/LLC nanocolloids is presented considering intermolecular interactions. The viscoelastic behavior and strong antibacterial activity (inhibition zone 49.2 mm) of LLCs and GQD/LLC nanocolloids make them valuable candidates for lubrication, cleaning, cosmetics and pharmaceutical applications.

Effect of Tinospora cordifolia on gestational diabetes mellitus and its complications.

Ayurvedic system of medicine uses giloy or guduchi, also known as Tinospora cordifolia (TC), to treat diabetes and related diseases like hyperglycemia and hyperlipididemia. However, its usage in gestational diabetes mellitus (GDM) is not well studied. The primary objective of the study was to examine the effects of water extract of TC called satva, essential oil, and hydroalcoholic (HA) extract on GDM and its complications and to explore their mechanism of action using mice model. We used streptozotocin-induced diabetes in pregnant mice as murine model and tested TC preparations for anti-GDM activities. Blood glucose, insulin, litter size, and placental weight were assessed. ELISA method was used to measure plasma insulin level to compute homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and homeostatic model assessment for assessing beta cell function (HOMA-Beta) levels to estimate insulin resistance, insulin sensitivity, and beta cell function respectively. TC-treated groups had significantly higher serum insulin levels, QUICKI, average litter size, and lower placental weight (p < .001). TC oil and HA extract increased pancreatic beta cell activity according to the level of HOMA-Beta. TC lowered placenta weight and increased litter size significantly compared to control group. Our findings suggest that TC preparations preserve pancreatic beta cells, increase insulin production, decrease insulin resistance, and improve beta cell function, hence preventing GDM. TC preparations also reduced placental weight and increased litter size in mice. Based on these results, we recommend the clinical trial and testing of TC preparations for management of GDM and associated complications. Refer graphical abstract (Figure S1).

A Comprehensive Review on Pharmacologically Active Phyto-Constituents from Hedychium species.

In this review, we describe and discuss the phytoconstituents present in Hedychium species and emphasize their potential as drug candidates. Though they are widely validated in vitro and in vivo models, to date, no efforts have been made to compile in a single review all the pharmacologically active phytoconstituents from Hedychium species, and their pharmacological and toxicity profile. In this study, we present a reinvestigation of the chemical constituents present in Hedychium species obtained from the essential oil and solvent extraction of the flowers, leaves and rhizomes under consideration. Key databases such as PubMed, Science Direct, Scopus, and Google Scholar amongst others were probed for a systematic search using keywords to retrieve relevant publications on this plant. An exhaustive electronic survey of the related literature on Hedychium species resulted in around 200 articles. Articles published between the years 1975-2021 were included. The studies conducted on either crude extracts, solvent fractions or isolated pure compounds from Hedychium species reported with a varied range of biological effects such as anti-inflammatory, analgesic, antidiabetic, potentially anti-asthmatic, and cytotoxic, among other related activities of the chemical constituents present in its essential oil and solvent extract deployed in this review. Traditional and herbal medication around the world that uses different parts of Hedychium species were considered for anti-inflammatory, skincare, analgesic, anti-asthmatic, anti-diabetic, antidotal uses, among others. These uses support the idea that chemical constituents obtained from solvent extraction may also exert the same action individually or in a synergistic manner. The review concluded that there is scope for computation and biological study to find out possible new targets for strengthening the potency and selectivity of the relevant compounds, and to find a commercial method for extraction of active pharmaceutical ingredients.

Interventions by pharmacists in out-patient pharmaceutical care.

Interventions by the pharmacists have always been considered as a valuable input by the health care community in the patient care process by reducing the medication errors, rationalizing the therapy and reducing the cost of therapy. The primary objective of this study was to determine the number and types of medication errors intervened by the dispensing pharmacists at OPD pharmacy in the Khoula Hospital during 2009 retrospectively. The interventions filed by the pharmacists and assistant pharmacists in OPD pharmacy were collected. Then they were categorized and analyzed after a detailed review. The results show that 72.3% of the interventions were minor of which 40.5% were about change medication order. Comparatively more numbers of prescriptions were intervened in female patients than male patients. 98.2% of the interventions were accepted by the prescribers reflecting the awareness of the doctors about the importance of the pharmacy practice. In this study only 688 interventions were due to prescribing errors of which 40.5% interventions were done in changing the medication order of clarifying the medicine. 14.9% of the interventions were related to administrative issues, 8.7% of the interventions were related to selection of medications as well as errors due to ignorance of history of patients. 8.2% of the interventions were to address the overdose of medications. Moderately significant interventions were observed in 19.4% and 7.5% of them were having the impact on major medication errors. Pharmacists have intervened 20.8% of the prescriptions to prevent complications, 25.1% were to rationalize the treatment, 7.9% of them were to improve compliance. Based on the results we conclude that the role of pharmacist in improving the health care system is vital. We recommend more number of such research based studies to bring awareness among health care professionals, provide solution to the prescription and dispensing problems, as it can also improve the documentation system, emphasize the importance of it, reduce prescribing errors, and update the knowledge of pharmacists and other health care professionals.

Immunotherapies: A Treasure Trove of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that falls under the umbrella of dementia and is characterized by the presence of enormously neurotoxic amyloid- beta (Aß) plaques and neurofibrillary tangles (NFTs) of tau protein inside the brain. AD remains an intractable global health challenge with limited therapeutic options. Early diagnosis, enabled by biomarkers and neuroimaging, is pivotal for optimizing treatment outcomes. Immunotherapeutic strategies, including monoclonal antibodies, active vaccination, and passive immunization, have been developed to target hallmark AD pathology, such as amyloid-beta aggregation. Here we summarized the emerging role of immunotherapies in the early stages of AD, shedding light on recent breakthroughs and clinical progress. Challenges, including treatment response variability and safety concerns, are discussed alongside evolving approaches, such as personalized immunotherapy and combinatorial treatments. This concise review underscores the promise of immunotherapies as a transformative approach to AD intervention, offering hope for a brighter future in the quest to combat this devastating neurodegenerative disease.

Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.