Naringin and temozolomide combination suppressed the growth of glioblastoma cells by promoting cell apoptosis: network pharmacology, in-vitro assays and metabolomics based study.

Introduction: Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches. However, the ability to treat patients effectively is usually limited by TMZ resistance. Naringin, a bioflavonoid with anti-cancer, antioxidant, metal-chelating, and lipid-lowering effects, has emerged as a promising therapeutic option. Methods: To explore the targets and pathways of naringin and TMZ in glioblastoma network pharmacology, cell line-based ELISA, flow cytometry, immunocytochemistry, western blotting, and LC-HRMS based metabolomics study were used. Results: The findings through the network pharmacology suggested that the key targets of naringin in the chemosensitization of glioblastoma would be Poly [ADP-ribose] polymerase 1 (PARP-1), O-6-Methylguanine-DNA Methyltransferase (MGMT), and caspases. The functional enrichment analysis revealed that these targets were significantly enriched in important pathways such as p53 signaling, apoptosis, and DNA sensing. Further, the results of the in-vitro study in U87-MG and T98-G glioblastoma cells demonstrated that TMZ and naringin together significantly reduced the percentage of viability and inhibited the DNA repair enzymes PARP-1 and MGMT, and PI3K/AKT which led to chemosensitization and, in turn, induced apoptosis, which was indicated by increased p53, caspase-3 expression and decreased Bcl2 expression. Additionally, a metabolomics study in T98-G glioblastoma cells using liquid chromatography high-resolution mass spectrometry (LC-HRMS) revealed downregulation of C8-Carnitine (-2.79), L-Hexanoylcarnitine (-4.46), DL-Carnitine (-2.46), Acetyl-L-carnitine (-3.12), Adenine (-1.3), Choline (-2.07), Propionylcarnitine (-1.69), Creatine (-1.33), Adenosine (-0.84), Spermine (-1.42), and upregulation of Palmitic Acid (+1.03) and Sphingosine (+0.89) in the naringin and TMZ treatment groups. Discussion: In conclusion, it can be said that naringin in combination with TMZ chemosensitized TMZ antiglioma response and induced apoptosis in tumor cells.

A Comprehensive Review on the Development of Titanium Complexes as Cytotoxic Agents.

After the discovery of cis-platin, the first metal-based anticancer drugs, budotitane, and titanocene dichloride entered clinical trials. These two classes of complexes were effective against those cell lines that are resistant to cisplatin and other platinum-based drugs. However, the main limitation of these complexes is their low hydrolytic stability. After these two classes, a third generation titanium based complex, i.e. diaminebis(phenolato)bisalkoxo, was invented, which showed more hydrolytic stability and high cytotoxicity than budotitane and titanocene dichloride. The Hydrolytic stability of complexes plays an important role in cytotoxicity. Earlier research showed that hydrolytically less stable complexes decompose rapidly into non-bioavailable moiety and become inactive. The mechanism of Ti(IV) complexes of diaminebis(phenolato)bisalkoxo is under investigation and is presumed to involve Endoplasmic Reticulum (ER) stress, which leads to apoptosis. The proposed mechanism involves the removal of ligands from the titanium complex and the binding of the Ti center to transferrin protein and its release inside the cell. Also, the structure of the ligand plays a key role in the cytotoxicity of complexes; as the bulkiness of the ligand increased, the cytotoxic nature of complexes decreased.

Impact of fluorosis on molecular predictors in pathogenesis of type 2 diabetes associated microvascular complications.

AIM: This review presents specific insights on the molecular underpinnings of the connection between fluorosis, type 2 diabetes, and microvascular complications, along with the novel biomarkers that are available for early detection. SUMMARY: Fluoride is an essential trace element for the mineralization of teeth and bones in humans. Exposure to higher concentrations of fluoride has harmful effects that significantly outweigh its advantageous ones. Dental fluorosis and skeletal fluorosis are the common side effects of exposure to fluoride, which affect millions of individuals globally. Alongside, it also causes non-skeletal fluorosis, which affects the population suffering from non-communicable diseases like diabetes by impacting the soft tissues and causing diabetic microvascular complications. Previous studies reported the prevalence range of these diabetic complications of neuropathy (3-65 %), nephropathy (1-63 %), and retinopathy (2-33 %). Fluoride contributes to the development of these complications by causing oxidative stress, cellular damage, degrading the functioning capability of mitochondria, and thickening the retinal vein basement. CONCLUSION: Early diagnosis is a prompt way of prevention, and for that, biomarkers have emerged as an innovative and useful technique. This allows healthcare practitioners and policymakers in endemic areas to comprehend the molecular complexities involved in the advancement of diabetic microvascular problems in the context of high fluoride exposure.

Development and Psychometric Validation of Population-Based Knowledge Attitudes and Practices-Questionnaire on Fluoride (PBKAP-QF).

Fluoride exposure is a global public health concern. Understanding the knowledge, attitudes, and practices (KAP) of affected populations is essential for effective community management. This study aimed to develop and validate a KAP questionnaire to assess fluoride and its risk in general population. An extensive literature review and focus group discussions were conducted to construct the questionnaire. Content validity was assessed using the Content Validity Index (CVI) based on expert feedback. Factor analysis was performed for final tool validation, and item characteristics were analyzed using IBM SPSS v. 27 and IBM AMOS v. 26. A total of 300 responses were collected. Initially, 41 items were included in the questionnaire, which were reduced to 25 after expert review. The final version included 19 items, with an I-CVI ranging from 0.80 to 1.00, indicating no issues with item difficulty or discrimination. Cronbach's alpha ranged from 0.88 to 0.90, demonstrating good internal consistency. The Kaiser-Meyer-Olkin (KMO) value was 0.848, and Bartlett's test (χ2 = 6860.978, df = 156, p < 0.01) confirmed data suitability for factor analysis. Three constructs were extracted with factor loadings greater than 0.5. Confirmatory factor analysis demonstrated a good model fit. This study developed and validated a robust 19-item KAP questionnaire for assessing knowledge, attitudes, and practices related to fluoride exposure. The tool demonstrated excellent reliability, validity, and internal consistency, supporting its use in guiding effective community-level management and public health interventions in fluoride-endemic areas.

Adsorption, Orientation, and Speciation of Amino Acids at Air-Aqueous Interfaces for the Direct Air Capture of CO2.

Amino acids make up a promising family of molecules capable of direct air capture (DAC) of CO2 from the atmosphere. Under alkaline conditions, CO2 reacts with the anionic form of an amino acid to produce carbamates and deactivated zwitterionic amino acids. The presence of the various species of amino acids and reactive intermediates can have a significant effect on DAC chemistry, the role of which is poorly understood. In this study, all-atom molecular dynamics (MD) based computational simulations and vibrational sum frequency generation (vSFG) spectroscopy studies were conducted to understand the role of competitive interactions at the air-aqueous interface in the context of DAC. We find that the presence of potassium bicarbonate ions, in combination with the anionic and zwitterionic forms of amino acids, induces concentration and charge gradients at the interface, generating a layered molecular arrangement that changes under pre- and post-DAC conditions. In parallel, an enhancement in the surface activity of both anionic and zwitterionic forms of amino acids is observed, which is attributed to enhanced interfacial stability and favorable intermolecular interactions between the adsorbed amino acids in their anionic and zwitterionic forms. The collective influence of these competitive interactions, along with the resulting interfacial heterogeneity, may in turn affect subsequent capture reactions and associated rates. These effects underscore the need to consider dynamic changes in interfacial chemical makeup to enhance DAC efficiency and to develop successful negative emission and storage technologies.

Uranyl (UO22+) structuring and dynamics at graphene/electrolyte interface.

The physicochemical phenomena at the solid/electrolyte interfaces govern various industrial processes ranging from energy generation, storage, and catalysis to chemical separations and purification. Adsorption-based solid/liquid extraction methods are promising for the selective and rapid separation of nuclear (such as uranium) and other critical materials. In this study, we quantified the adsorption, complexation, and dynamics of UO22+ ions on the graphene surface in various electrolyte media (LiNO3, NaNO3 and CsNO3) using all-atom molecular dynamics simulations, in combination with network theory based subensemble analysis, enhanced sampling, and temporal analysis. We observe that the choice of background electrolyte impacts the propensity of UO22+ adsorption on the graphene surface, with LiNO3 being the most favorable at both low and high uranyl-nitrate concentrations. Even though UO22+ primarily retained its coordination with water and interacted via the outer-sphere mechanism with graphene, the interfacial segregation of NO3- increased the number of contact ion pairs (CIPs) between UO22+ and NO3- ions, and the residence times of UO22+ within the interfacial region. This study provides a fundamental understanding of the structure and dynamics of UO22+ on the solid surface necessary to design advanced adsorption-based separation methods for energy-relevant materials.

Reproductive toxicity perspectives of nanoparticles: an update.

INTRODUCTION: The rapid development of nanotechnologies with their widespread prosperities has advanced concerns regarding potential health hazards of the Nanoparticles. RESULTS: Nanoparticles are currently present in several consumer products, including medications, food, textiles, sports equipment, and electrical components. Despite the advantages of Nanoparticles, their potential toxicity has negative impact on human health, particularly on reproductive health. CONCLUSIONS: The impact of various NPs on reproductive system function is yet to be determined. Additional research is required to study the potential toxicity of various Nanoparticles on reproductive health. The primary objective of this review is to unravel the toxic effects of different Nanoparticles on the human reproductive functions and recent investigations on the reproductive toxicity of Nanoparticles both in vitro and in vivo.

A Study Comparing Centchroman and Evening Primrose Oil in the Treatment of Benign Breast Disease.

Introduction: Females seeking medical attention at breast clinics commonly present with nonmalignant breast conditions, including nonspecific breast pain or distinct masses like fibroadenomas. Due to its variability, it may be difficult to quantify breast pain. The purpose of the research was to compare centchroman and evening primrose oil to identify a cost-effective, secure, and efficient treatment for benign breast disease. Material and Methods: In this prospective hospital-based observational study, 100 breast diseases with or without lumpiness for 1 year were included and divided into two groups with 50 cases each, Group-A (Centchroman) and Group-B (Evening primrose oil). Results: Centchroman exhibited a significantly greater treatment response for alleviating pain-free mastalgia compared to evening primrose oil. Additionally, centchroman showed an excellent response (P < .05). Among participants with mastalgia, centchroman significantly reduced the number of mastalgia patients with tender nodularity post-treatment (P = .035) than evening primrose oil. On the basis of fibroadenoma, partial and complete response was significantly seen in higher number of cases in the centchroman group (P = .007). Conclusion: Centchroman therapy demonstrates that the treatment for benign breast disease is safe, effective, and economical.

Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.

Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.

GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

BACKGROUND: Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer's disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer's disease. AIM: This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD. METHODS: This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD. RESULTS: The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions. CONCLUSION: With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer's patients.

Reactive Oxygen Species and Mitochondrial Calcium's Roles in the Development of Atherosclerosis.

In the last decade, there has been increasing evidence connecting mitochondrial dysfunction to the onset and advancement of atherosclerosis. Both reactive oxygen species (ROS) and the disruption of mitochondrial calcium (Ca2+) regulation have garnered significant attention due to their involvement in various stages of atherosclerosis. This abstract discusses the potential therapeutic applications of targeting mitochondrial calcium (Ca2+) and reactive oxygen species (ROS), while also providing an overview of their respective roles in atherosclerosis. The abstract underscores the importance of mitochondrial Ca2+ homeostasis in cellular physiology, including functions such as energy production, cell death signaling, and maintaining redox balance. Alterations in the mitochondria's Ca2+ handling disrupt all these procedures and speed up the development of atherosclerosis. Reactive oxygen species (ROS), generated during mitochondrial respiration, are widely recognized as significant contributors to the development of atherosclerosis. Through modulating the function of calcium ion (Ca2+) transport proteins, ROS can impact the regulation of mitochondrial Ca2+ handling. These oxidative modifications lead to vascular remodeling and plaque formation by impairing endothelial function, encouraging the recruitment of inflammatory cells, and promoting smooth muscle cell proliferation. Preclinical investigations indicate that interventions aimed at regulating the production and elimination of reactive oxygen species (ROS) hold promise for mitigating atherosclerosis. Targeting mitochondrial processes represents a prospective therapeutic strategy for addressing this condition. Further research is necessary to elucidate the intricate molecular mechanisms associated with mitochondrial dysfunction in atherosclerosis and develop effective therapeutic strategies to decelerate disease progression.

Effect of naringin on sodium fluoride­induced neurobehavioral deficits in Wistar rats.

There is a lack of treatment for the detrimental effects of fluorosis. Sodium fluoride at a concentration of 10 ppm induces stress, depression and memory impairment in adult Wistar rats. Naringin, a flavanone glycoside isolated from citrus fruits such as lemons and oranges, possesses anti-inflammatory, antioxidant and neuroprotective properties; therefore, it was used for treatment of fluoride induced toxicity in the present study. Adult Wistar rats were divided into eight groups (n=8). The normal control (NOR) group was provided with normal tap water. The sodium fluoride (FLU)10 group received water containing 10 ppm sodium fluoride for 60 days. The treatment groups (FLU10NAR100 and FLU10NAR50) received drinking water with 10 ppm sodium fluoride ad libitum along with Naringin 100 and 50 mg/kg body weight (bw) per oral gavage, respectively. The NAR100 and NAR50 groups received Naringin 100 and 50 mg/kg bw. The PRONAR100 and PRONAR50 groups received Naringin 100 and 50 mg/kg bw for the first 15 days and then subsequently received FLU10 ppm for 60 days (total of 75 days). All animals were subjected to behavioural tests consisting of the open field test (OFT), forced swim test (FST) and novel object recognition test (NORT). After euthanasia, the hippocampus and prefrontal cortex were stained with Cresyl violet. To measure the oxidative stress caused by fluoride and its effect on antioxidant levels, estimation of reduced glutathione (GSH) by Ellman's method, lipid peroxidation (LPO) measured in terms of the MDA:thiobarbituric acid reaction and catalase was performed. To evaluate the effect of fluoride on activity of acetylcholine, estimation of acetylcholinesterase (AChE) by Ellman's method was performed. In NORT and FST, significant changes (P<0.05) were present in the FLU10NAR100 and FLU10NAR50 groups compared with the FLU10 group, showing recovery from memory deficit and depression. The OFT results were insignificant. The LPO was reduced in all the other groups except the FLU10 group, with statistically significant changes. Catalase activity was significantly lower in FLU10 as compared with the NAR100, NAR50, PRONAR100 and PRONAR50 groups. GSH and AChE activities did not show significant changes as compared with the FLU10 group. The CA3 and prefrontal cortex viable and degenerated neuron count in the FLU10 group were insignificant compared with all other groups, except for the NAR100 and NAR50 groups. Thus, Naringin can be a useful drug to avoid the neurological effects of fluoride.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

Epigenetic modifications in Parkinson's disease: A critical review.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder expected to increase by over 50% by 2030 due to increasing life expectancy. The disease's hallmarks include slow movement, tremors, and postural instability. Impaired protein processing is a major factor in the pathophysiology of PD, leading to the buildup of aberrant protein aggregates, particularly misfolded α-synuclein, also known as Lewy bodies. These Lewy bodies lead to inflammation and further death of dopaminergic neurons, leading to imbalances in excitatory and inhibitory neurotransmitters, causing excessive uncontrollable movements called dyskinesias. It was previously suggested that a complex interplay involving hereditary and environmental variables causes the specific death of neurons in PD; however, the exact mechanism of the association involving the two primary modifiers is yet unknown. An increasing amount of research points to the involvement of epigenetics in the onset and course of several neurological conditions, such as PD. DNA methylation, post-modifications of histones, and non-coding RNAs are the primary examples of epigenetic alterations, that is defined as alterations to the expression of genes and functioning without modifications in DNA sequence. Epigenetic modifications play a significant role in the development of PD, with genes such as Parkin, PTEN-induced kinase 1 (PINK1), DJ1, Leucine-Rich Repeat Kinase 2 (LRRK2), and alpha-synuclein associated with the disease. The aberrant epigenetic changes implicated in the pathophysiology of PD and their impact on the design of novel therapeutic approaches are the primary focus of this review.

Analysis of the metabolic profile of humans naturally exposed to RF-EM radiation.

INTRODUCTION: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things. OBJECTIVES: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations. METHODS: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30). RESULTS: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis. CONCLUSION: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population.

Obesity and Depression: Common Link and Possible Targets.

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments.

Supine tubeless upper pole PCNL under spinal anaesthesia: Safety, feasibility and outcomes from a tertiary endourology centre.

Objective: Supine Percutaneous Nephrolithotomy (PCNL) is being taken up by many urologists in recent times, but there is a tendency to shift to prone PCNL for upper pole puncture. We analyzed the safety, feasibility and outcomes of upper pole access in Supine Percutaneous Nephrolithotomy (sPCNL). Materials and methods: A retrospective review of all patients undergoing sPCNL at a tertiary care center was done from January 2021 to December 2022. Data collection was done from the maintained imaging, laboratory and hospital records. All cases with complete data on upper pole access were included. Data analysis was done with Xlstat2021. Results: 50 patients with upper pole access were included (64%, 32 with single access and 36%, 18 with multiple accesses). The mean stone size was 23.88 ± 9.99, mean HU was 1093 ± 232.83, and the mean operative duration was 67.92 ± 34.62. Stone clearance rate was 98.82%, with all procedures performed tubeless.The mean haemoglobin drop was 0.75 ± 0.42 gm/dl with 2 (4%) patients needing a blood transfusion. The overall complication rate was 22% with only 1 Clavien Dindo III complication (1 pleural injury and hydrothorax needing USS guided aspiration) and others being Clavien Dindo I/II complications. Conclusion: Supine PCNL is a feasible and safe approach for upper pole access. While the procedure can be done tubeless, these procedures must be done in experienced endourology units.

Monopolar Transurethral Enucleoresection of Prostate: Feasibility of Modified Nesbit's Enucleoresection with Apical Release.

Background: Transurethral resection of the prostate (TURP) has been the standard surgical treatment for Benign Hyperplasia of the Prostate (BPH) for decades. Our objective was to evaluate the outcome of our new technique: Monopolar Transurethral Enucleoresection of the Prostate (TUERP) with apical release (bring it all to centre). Methods: A prospective study of all cases undergoing TUERP at a tertiary centre from January 2020 to October 2022 was performed. Patient demographics, intraoperative variables and postoperative results along with follow-up data were collected. Data of all the cases who had completed a one-year follow-up post-surgery were included and analysed. Results: A total of 240 patients with complete data including a one-year follow-up were included. Mean prostatic volume was 55.3 ± 11.6 gm, and 28 (11.67%) cases were >100 gm. The mean operative time was 31.7 ± 7.6, and mean haemoglobin drop at 24 h was 0.73 ± 1.21 gm/dL. The overall complication rate was 16.67%, with only two (0.83%) Clavien-Dindo III complications (haematuria and clots needing evacuation) and the other complications being Clavien-Dindo I/II complications. Sustained improvement at 1 year of follow-up was noted: Qmax: 25.2 ± 5.6 mL/s, IPSS: 4.7 ± 2.5 and PVR: 22.5 ± 9.6 mL. Conclusions: Monopolar TUERP with a modified Nesbit's enucleoresection with apical release can be considered a promising technique, which needs further studies to be validated with appropriate comparisons.

SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs.

Cardiovascular diseases (CVDs) can be described as a global health emergency imploring possible prevention strategies. Although the pathogenesis of CVDs has been extensively studied, the role of mitochondrial dysfunction in CVD development has yet to be investigated. Diabetic cardiomyopathy, ischemic-reperfusion injury, and heart failure are some of the CVDs resulting from mitochondrial dysfunction Recent evidence from the research states that any dysfunction of mitochondria has an impact on metabolic alteration, eventually causes the death of a healthy cell and therefore, progressively directing to the predisposition of disease. Cardiovascular research investigating the targets that both protect and treat mitochondrial damage will help reduce the risk and increase the quality of life of patients suffering from various CVDs. One such target, i.e., nuclear sirtuin SIRT6 is strongly associated with cardiac function. However, the link between mitochondrial dysfunction and SIRT6 concerning cardiovascular pathologies remains poorly understood. Although the Role of SIRT6 in skeletal muscles and cardiomyocytes through mitochondrial regulation has been well understood, its specific role in mitochondrial maintenance in cardiomyocytes is poorly determined. The review aims to explore the domain-specific function of SIRT6 in cardiomyocytes and is an effort to know how SIRT6, mitochondria, and CVDs are related.

Clinical Profile of Triple-Negative Breast Cancer: A Hospital-Based Study.

Introduction Triple-negative breast cancer (TNBC) is a new concept and an important area of investigation. In Western country's literature, different studies reported on TNBC and all indicated the poor prognostic aspect of this molecular subtype over other types of breast cancer. However, there is a scarcity of comprehensive data from India. Hence, the present study was carried out to look at the epidemiological and clinical characteristics of TNBC in the Indian population. Methods The present study was performed between January 2020 and June 2021 at a tertiary care hospital in Eastern India. A total of 150 patients with TNBC were enrolled in the study. The epidemiological and clinical features of enrolled patients were collected and reviewed. Results The median age of patients at TNBC presentation was 45.53 years (24 to 74 years). The median tumor size was reported to be 5.32 cm. Of 150 patients, 94(62.67%) showed enlarged lymph nodes and 56 (37.33%) patients had no lymph node enlargement. In the present study, 85 (56.67%) patients were in the pre/perimenopausal stage at presentation, whereas 65 (43.33%) patients were in the postmenopausal stage. Upon evaluating the spread of TNBC, it was observed that a maximum of patients 60 (40%) were at the T4 stage and 56 (37.33%) at the N0 condition. The clinical staging of TNBC reported a maximum of 74 (49.33%) patients at the IIA, and IIB stages followed by 53 (35.33%) patients at the IIIA, IIIB, and IIIC stages and a minimum of 11 (7.33%) patients at stage IV. Only five (3.33%) patients were reported with a family history of breast cancer. Of all patients, 126 (84%) had detected early breast cancer thereby applicable for surgery at the time of presentation, whereas 71 (47.33%) patients were eligible for radiation therapy and 138 (92%) patients received chemotherapy. A total of 112 (74.67%) patients were found alive after 24 months of follow-up, 22 (4.67%) patients were observed with remission, and 11 (7.33%) patients died due to TNBC progression. During the course of follow-up, five (3.33%) patients were lost in the study.  Conclusion TNBC is an aggressive malignancy that has a high risk of systemic relapses in the first two years after diagnosis. For more mature evidence on TNBC, longer follow-up of patients is necessary.