Estimating the annual production data of bidi sticks in India using the "back-of-the-envelop-method".

The Indian bidi industry is largely unorganised with poorly implemented regulations along with laxed taxations. The unaccounted production of bidi sticks might potentiate its illicit circulation and therefore, unchecked availability to the minors. Specific production estimates may lead to stricter compliance with the existing regulatory norms. Due to the paucity of evidence and wide variability in production numbers, this estimation of the exact number of bidi sticks produced annually within the country was conducted. The annual number of produced sticks were estimated using the available literature till May 2023, on: a) the quantity of auctioned tendu leaves, b) number of bidi rollers, and c) bidi tobacco cultivated. Around 10 % attritions were considered during each stage of the manufacturing process to arrive at the production estimates. Annual bidi stick production was estimated as a) 319.83 billion, b) 600 billion to 1 trillion, and c) 974 billion to 1.19 trillion. This research provides a crucial estimate of the alarming number of bidi sticks produced and address the significant gap in reliable data of production figures. These insights underscore the urgency for stringent policy measures and regulation of bidi industry to safeguard health and curtail illicit practices.

Bow Hunter Phenomenon From Advanced Cerebrovascular Disease Treated With Subclavian Artery Stenting and Carotid Endarterectomy.

Bow Hunter syndrome (BHS) is a rare disorder characterized by mechanical occlusion of the vertebral artery (VA) during neck rotation, resulting in symptomatic, transient, and positional vertebrobasilar insufficiency. We describe a case of a 76-year-old female who presented with dizziness and right ear tinnitus triggered by right head rotation. Her symptoms would immediately resolve upon returning her head to the neutral position. CT angiogram showed 80% stenosis of the left subclavian artery origin, 50%-70% stenosis of the proximal right internal carotid artery (ICA), and near occlusive stenoses of the origins of the bilateral VAs. After failing conservative management, the patient was treated with left subclavian artery stenting, followed by a right carotid endarterectomy (CEA) 6 weeks later. Follow-up at 1 month showed resolution of paroxysmal symptoms and no neurological sequelae. To our knowledge, there have not yet been reported cases of patients with concurrent BHS, subclavian artery stenosis, and carotid artery stenosis. We suggest that global revascularization via subclavian artery stenting and CEA may be considered as treatment for patients with BHS complicated by other cerebrovascular disease secondary to stenoses of the ICA and subclavian artery. This approach obviates the need for more complex surgery or endovascular intervention of the VA.

Oncogenic potential of SARS-CoV-2-targeting hallmarks of cancer pathways.

The 2019 outbreak of SARS-CoV-2 has caused a major worldwide health crisis with high rates of morbidity and death. Interestingly, it has also been linked to cancer, which begs the issue of whether it plays a role in carcinogenesis. Recent studies have revealed various mechanisms by which SARS-CoV-2 can influence oncogenic pathways, potentially promoting cancer development. The virus encodes several proteins that alter key signaling pathways associated with cancer hallmarks. Unlike classical oncogenic viruses, which transform cells through viral oncogenes or by activating host oncogenes, SARS-CoV-2 appears to promote tumorigenesis by inhibiting tumor suppressor genes and pathways while activating survival, proliferation, and inflammation-associated signaling cascades. Bioinformatic analyses and experimental studies have identified numerous interactions between SARS-CoV-2 proteins and cellular components involved in cancer-related processes. This review explores the intricate relationship between SARS-CoV-2 infection and cancer, focusing on the regulation of key hallmarks driving initiation, promotion and progression of cancer by viral proteins. By elucidating the underlying mechanisms driving cellular transformation, the potential of SARS-CoV-2 as an oncovirus is highlighted. Comprehending these interplays is essential to enhance our understanding of COVID-19 and cancer biology and further formulating strategies to alleviate SARS-CoV-2 influence on cancer consequences.

New Insights into the Diagnosis, Monitoring, and Management of Antenatal Hydronephrosis, Aiming to Refine Treatment Protocols: A Clinical Study.

Background: Antenatal hydronephrosis (ANH) is a common prenatal finding that requires careful evaluation to determine appropriate management strategies. The variability in outcomes underscores the need for refined diagnostic and monitoring protocols to differentiate between cases necessitating intervention and those likely to resolve spontaneously. Materials and Methods: A prospective clinical study was conducted involving 150 pregnant women diagnosed with ANH between gestational weeks 18 to 24. Prenatal ultrasounds were performed at regular intervals to monitor renal pelvic dilatation. Postnatal evaluations included renal ultrasound, voiding cystourethrography, and nuclear renal scans to assess renal function and identify associated anomalies. Management decisions were based on standardized criteria including degree of hydronephrosis, presence of associated anomalies, and renal function. Results: Of the 150 cases, 80 (53.3%) resolved spontaneously during the prenatal period, while 70 (46.7%) required postnatal intervention. Among the intervention group, 45 cases (64.3%) required surgical correction for persistent hydronephrosis or associated anomalies, while the remaining 25 cases (35.7%) were managed conservatively with close monitoring. Arbitrarily, the mean anteroposterior renal pelvic diameter (APRPD) in the resolved group was 5.2 mm, compared to 10.6 mm in the intervention group. The median postnatal follow-up duration was 24 months. Conclusion: This study highlights the importance of systematic evaluation and monitoring in managing ANH. While a significant proportion of cases resolve spontaneously, a careful assessment of associated anomalies and renal function is crucial in identifying cases requiring intervention. The arbitrary APRPD values presented underscore the potential for establishing diagnostic thresholds to guide clinical decision-making. Refinement of treatment protocols based on such parameters can improve outcomes and reduce unnecessary interventions in infants with ANH.

Endovascular Embolization of Aneurysmal Renal Arteriovenous Malformation.

Renal arteriovenous malformations (AVM) represent an uncommon vascular condition characterized by an abnormal direct communication between an intrarenal artery and vein. Though asymptomatic in many individuals, treatment is often indicated if the AVM causes flank pain, hematuria, or medically refractory hypertension, or if there is an associated renal artery aneurysm. We present a case of a large right renal AVM with associated renal artery aneurysm and large varix which was incidentally found on magnetic resonance imaging of the spine. Endovascular and open surgical options were considered, including ex-vivo renal vascular reconstruction and nephrectomy. The patient was successfully treated with endovascular embolization of the AVM with coil packing of the arterial aneurysm and inflow artery. The patient recovered uneventfully with well-maintained renal function and blood pressure control. We review and discuss the literature on the etiology and treatment options for renal AVM.

End TB strategy: Role of tobacco control.

Tobacco use and Tuberculosis (TB) presents a huge public health challenge globally. Tobacco and TB have consistent and strong epidemiological evidence with smokers having higher odds of TB infection, disease, mortality, delayed diagnosis etc. Overall, limited evidence exists about the extent of TB-tobacco integration. The aim of the current short communication is to highlight comprehensive strategy for addressing TB-tobacco comorbidities.

Antifungal susceptibility pattern of Candida auris strains: Analysis of clinical strains in a tertiary-care educational university hospital.

Herein, we aimed to investigate the antifungal susceptibility pattern of Candida auris clinical strains in our setting Bahrain Oncology Center-King Hamad University Hospital-Bahrain. C. auris strains isolated from different clinical specimens in the Microbiology Laboratory from October-2021 to November-2022 were evaluated. Species-level identification of fungi was performed by MALDI-TOF (Bruker, Germany). Minimum inhibitory concentration (MIC) was determined either by E-test strips or by MICRONAUT MIC system based on CDC guidelines for C. auris antifungal interpretation. Fluconazole, amphotericin-B, voriconazole, and caspofungin susceptibility data of the clinical strains were analyzed. A total of 40 clinical isolates were included: 25% were blood culture isolates, 65% were urinary, and 10% were soft tissue isolates. Only 29 strains could be tested for amphotericin-B and 32 for voriconazole. Overall resistance pattern was as follows: 100% resistance to fluconazole, 2.5% resistance to caspofungin, and 0% resistance to amphotericin b. Median voriconazole MIC was 0.015 ug/ml (min 0.08, max= 0.064 ug/ml). We had no fluconazole-sensitive strain and only one caspofungin-resistant strain. A single isolate (2.5%), which was associated with candidemia, demonstrated resistance to two antifungal agents: fluconazole and caspofungin. No triple or quadruple drug resistant strain existed.

Increased taxes and regulation of Indian cigarillos (bidi) industry: Effects on revenue and years of life lost.

INTRODUCTION: Indian cigarillos (bidi) are low-cost alternatives to cigarettes with only 22% imposed taxes, and turnover of upto INR 4 million per annum exempted from taxation. This paper estimates revenue implications and potential loss of life years (YLLs) averted, if bidi industry is subjected to increased regulations and taxation. METHODS: Revenue estimated at 10% increased regulation and 100% regulation were calculated, followed by estimates at taxes equivalent to cigarettes and World Health Organization - Framework Convention on Tobacco Control (WHO-FCTC) recommendation. Price elasticity was considered to assess demand. Price change in separate fractions (previously regulated and unregulated) were calculated to obtain potential YLLs averted. RESULTS: Current revenue of USD 59.25 million is projected to increase to USD 179.25 million with 695,159 averted YLLs at cigarette equivalent taxes and 10% increased regulation; USD 639.38 million with 4,527,597 averted YLLs with 100% regulation; USD 54.75 million, at WHO recommended taxes with 2,233,740 YLLs averted at 10% increased regulation, and 10,486,192 YLLs at 100% regulation. CONCLUSION: Proposed estimates are inline with WHO recommendations as they consider price elasticity and suggest substantial increase in revenue, while averting YLLs. A national action is needed to drive the policy decisions towards increased regulation and taxation and revision of India's tobacco control legislation. IMPLICATIONS: Our study presented empirical evidence of how the currently underutilized tool of taxation, as proposed in the WHO-FCTC, can be utilized to decrease bidi smoking prevalence and save measurable life years while generating government revenue simultaneously. While the revenue statistics counter the misleading tobacco industry narratives, the projected reduction in mortality will be seen as an irrefutable driving force for policy reforms, targeted at strategic increase in regulation and taxation of the traditional Indian cigarillos industry.

Fisetin induces G2/M phase arrest and caspase-mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC.

The anticancer potential and associated mechanisms of flavonoid fisetin are yet to be fully investigated on human head and neck squamous cell carcinoma (HNSCC). In the present study, fisetin (25-75 µM for 24-48 h) dose-dependently inhibited growth and induced death in HNSCC Cal33 and UM-SCC-22B cells, without showing any death in normal cells. Fisetin (25-50 µM) induced G2/M phase arrest via decrease in Cdc25C, CDK1, cyclin B1 expression, and an increase in p53(S15). A concentration-dependent increase in fisetin-induced DNA damage and apoptosis in HNSCC cells was authenticated by comet assay, gamma-H2A.X(S139) phosphorylation, and marked cleavage of PARP protein. Interestingly, fisetin-induced cell death occurred independently of p53 and reactive oxygen species production. The activation of JNK and inhibition of PI3K/Akt, ERK1/2, EGFR, and STAT-3 signaling were identified. Further, fisetin-induced apoptosis was mediated, in part, via p21Cip1 and p27Kip1 cleavage by caspase, which was reversed by z-VAD-FMK, a pan-caspase inhibitor. Subsequently, fisetin was also found to induce autophagy; nevertheless, autophagy attenuation exaggerated apoptosis. Oral fisetin (50 mg/kg body weight) treatment to establish Cal33 xenograft in mice for 19 days showed 73% inhibition in tumor volume (p < 0.01) along with a decrease in Ki67-positive cells and an increase in cleaved caspase-3 level in tumors. Consistent with the effect of 50 µM fisetin in vitro, the protein levels of p21Cip1 and P27Kip1 were also decreased by fisetin in tumors. Together, these findings showed strong anticancer efficacy of fisetin against HNSCC with downregulation of EGFR-Akt/ERK1/2-STAT-3 pathway and activation of JNK/c-Jun, caspases and caspase-mediated cleavage of p21Cip1 and p27Kip1.

Long-term follow-up in high-grade meningioma and outcome analysis.

Objectives: The determinants of progression-free survival (PFS) and overall survival (OS) for higher-grade meningiomas have not been clearly established and to summarize the long-term clinical outcome for patients with grade 2 or 3 meningioma and assess the PFS and OS factors. Materials and Methods: The study included all individuals, who had undergone surgical removal of cerebral meningiomas between 2005 and 2020 and whose histological results suggested a World Health Organization (WHO) grade 2 or grade 3 diseases. Kaplan-Meier curves are plotted to examine tumor control and OS after the follow-up. The reverse Wald logistic regression and Mantel-Cox test were used in multivariate analysis for tumor recurrence and mortality. Results: There were 94 individuals enrolled with 82 having WHO grade 2 tumors and 12 having WHO grade 3 lesions. Gross total resection of the tumor was present in 73 patients (78%), and adjuvant radiotherapy (RT) was administered to 43 (45.7%) individuals. During the course of the study, 17 patients died. The WHO grade of the tumor, the extent of resection, and the absence of bone involvement were all independent predictors of better survival in a multivariate analysis. Furthermore, whereas adjuvant RT after surgery enhanced survival, it was not statistically significant (hazard ratios [95% confidence interval CI] = 1.91 [0.15-23.52] [P = 0.61]). Conclusion: The degree of tumor excision is the strongest predictor of PFS and OS. In the event of a recurrence, rather than opting for upfront radiation, a second surgery with the goal of maximum safe resection should be performed.

Effect of Mirabegron in Men With Overactive Bladder and Erectile Dysfunction: A Prospective Observational Study.

BACKGROUND: As it has been observed that the erect penis has been the epitome of virility for the male community for decades, it became necessary to search for alternative treatments for the cause. So, the study was performed to evaluate the potential impact of mirabegron in men with mild to moderate erectile dysfunction (ED) and overactive bladder (OAB). METHODS: It was a prospective, observational study that was carried out at the Department of Urology at Rajendra Institute of Medical Sciences, Ranchi, for a duration of two years and included a total of two hundred fifty patients. The individuals included had a diagnosis of mild to moderate erectile dysfunction (ED) along with symptoms of OAB. The overactive bladder questionnaire (OAB-q) score and the International Index of Erectile Dysfunction-5 (IIEF-5) score were used, respectively, to measure the impact of mirabegron on ED and OAB. Then, the changes in ED and OAB were evaluated at two, four, eight, and 12 weeks. RESULTS: Among the total 250 patients recruited, around 32.5% of them had mild ED, 17.5% were diagnosed with mild to moderate ED, and 50% suffered from moderate ED. The IIEF-5 scores improved by four points or more in 86.25%, 91.25%, and 71.25% of patients after four, eight, and 12 weeks, respectively. OAB-q scores were likewise shown to decline in the fourth (13.1 ± 4.3) and eighth (12.8 ± 4.2) weeks when compared to the baseline (17.4 ± 5.5). Also, adverse events reported did not hamper the progress of the study. CONCLUSION: The study concluded that mirabegron has a beneficial impact on controlling OAB symptoms among men diagnosed with mild to moderate ED. The effects last for only eight weeks, and then they decline. Furthermore, mirabegron was well-tolerated among patients and had no safety concerns with its use.

Obturator Nerve Block: An Anatomical Perspective.

Background A comprehensive understanding of the anatomy of the obturator nerve after its emergence from the obturator foramen is essential when undertaking an obturator nerve block effectively. This study was conducted to provide precise anatomical guidance of the obturator nerve block with surface landmarks in the inguinal region. Materials and methods A cross-sectional observational study was carried out on 34 dissected embalmed cadaveric lower limbs to investigate anatomic variability of obturator nerve localization concerning bony/ligamentous landmarks viz. the pubic tubercle, anterior superior iliac spine, inguinal ligament, and femoral artery as well as the adductor longus. Results The pubic tubercle and inguinal ligament were found to be the "least variable indicator" and palpable landmark for localization of the main trunk of the obturator nerve exhibiting lesser standard deviation of the mean distance from the obturator nerve exit. Among the soft tissue (vessel/muscle) parameters, the shortest distance of the adductor longus muscle from the obturator nerve exit was found to have the lowest standard deviation, thus making it the most reliable parameter for obturator nerve localization. Conclusion High anatomic variability in the obturator nerve's localization does exist, and this explains the difficulty frequently encountered in the application of regional anesthetic techniques. The pubic tubercle and inguinal ligament points were found to be the least variable and most reliable landmarks for localization of the main trunk of the obturator nerve.

Competence of algal consortia under municipal wastewater: remediation efficiency, photosynthetic performance, antioxidant defense mechanisms and biofuel production.

Utilizing monoalgal species for wastewater treatment is facing tremendous challenges owing to changing wastewater complexity in terms of physico-chemical characteristic, nutrient and metal concentration. The environmental conditions are also fluctuating therefore, the formation of robust system is of utmost importance for concomitant sustainable wastewater treatment and bioenergy production. In the present study, the tolerance and adaptability potential of algal consortia-1 (Chlorococcum humicola and Tetradesmus sp.) and consortia-2 (Chlorococcum humicola, Scenedesmus vacuolatus and Tetradesmus sp.) treated with municipal wastewater were examined under natural environmental conditions. The results exhibited that consortia-2 was more competent in recovering nitrate-nitrogen (82.92%), phosphorus (70.47%), and heavy metals (31-73.70%) from municipal wastewater (100%) than consortia-1. The results further depicted that total chlorophyll, carbohydrate, and protein content decreased significantly in wastewater-treated consortia-1 as compared to consortia-2. However, lipid content was increased by 4.01 and 1.17 folds in algal consortia-1 and consortia-2 compared to their respective controls. Moreover, absorption peak at 1740.6 cm-1 reflected higher biofuel-producing potential of consortia-1 as compared to consortia-2 as confirmed through FTIR spectroscopy. The results also revealed that consortia-2 showed the highest photosynthetic performance which was evident from the increment in the active photosystem-II reaction center (1.724 ± 0.068), quantum efficiency (0.633 ± 0.038), and performance index (3.752 ± 0.356). Further, a significant increase in photosynthetic parameters was observed in selected consortia at lag phase, while a noteworthy decline was observed at exponential and stationary phases in consortia-1 than consortia-2. The results also showed the maximum enhancement in ascorbic acid (2.43 folds), proline (3.34 folds), and cysteine (1.29 folds) in consortia-2, while SOD (1.75 folds), catalase (2.64 folds), and GR (1.19 folds) activity in consortia-1. Therefore, it can be concluded that due to remarkable flexibility and photosynthetic performance, consortia-2 could serve as a potential candidate for sustainable nutrient resource recovery and wastewater treatment, while consortia-1 for bio-fuel production in a natural environment. Thus, formation of algal consortia as the robust biosystem tolerates diverse environmental fluctuations together with wastewater complexity and ultimately can serve appropriate approach for environmental-friendly wastewater treatment and bioenergy production.

Comparison of Perioperative Complication Rates of Total Extraperitoneal and Transabdominal Preperitoneal Repairs in Primary Inguinal Hernia.

Background: Hernia may be defined as a protrusion of viscus through layers anatomically designed to contain that viscus. Most abdominal hernias occur at well-described sites of potential weakness. Repair of inguinal hernia is one of the most common operations in general surgery. Objectives: To compare the perioperative complication rates of total extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) repairs of primary inguinal hernias. Materials and Methods: It is a randomised comparative study, conducted at the department of general surgery. A total of 50 patients were included and divided into two groups with 25 in each. Group A represents the laparoscopic TEP repair and group B represents the laparoscopic TAPP repair. Patients above 18 years with primary unilateral inguinal hernia were included. Patients having complicated inguinal hernia and history of previous abdominal surgery were excluded. Results: We observed that hernia occurrence is more common in the 31-50 years of age group and right-sided hernia is more common. Scrotal oedema and conversion to open surgery chances are similar in both TEP and TAPP groups. The duration of surgery in TEP is significantly higher as compared to TAPP. Patients who underwent TEP experienced less pain as compared to TAPP as per visual analogue scale. Postoperative hospital stay and time taken to resume the routine activity were significantly less in case of TEP. Conclusion: TEP is preferred over TAPP for laparoscopic hernia repair because it preserves the peritoneal integrity and has lesser postoperative pain. The early recovery and return to the routine work were seen with the patient treated with the TEP and also showed better visual analogue score than the TAPP repair group.

Complementary and Alternative Medicine/Therapy for Tobacco Cessation in India: A Secondary Analysis of GATS-1 and 2.

Background: India has nearly 267 million adult tobacco users, with a slowly improving quitting rate. Among the many approaches to quitting the habit, such as counseling, nicotine replacement therapy, nicotine patch or gum, and prescribed allopathic medicines. Complementary and alternative medicine/therapy (CAM), a thousand-year-old practice in India, may also prove to be a potential method in tobacco cessation; however, there is scarce literature on the extent of use of CAM among tobacco users who attempt to quit the habit. Therefore, this study attempts to examine the potential of CAM as a strategy for tobacco control in India. Material and Methods: We undertook a secondary analysis of the data from both rounds of the Global Adult Tobacco Survey (GATS 2009 and 2016). The dependent variable included in the analysis was the use of traditional medicine as a method for quitting tobacco in three types of users-smokers, smokeless tobacco users, and dual users. The prevalence of CAM use was reported, and Chi-square test was applied to find the factors significantly associated with the use of CAM among tobacco users considering a P value of 0.05 to be statistically significant. Results: The overall prevalence of traditional medicine use for GATS-1 was observed to be more among dual users (4%), while for GATS-2, it was highest among smokers (3%). For both rounds of the GATS survey, the use of traditional medicine was found to be higher among males, rural residents, users with no education or less than primary education, and the eastern region. Conclusions: CAM has a promising potential for supporting tobacco cessation provided a concerted effort is undertaken to standardize pharmacopeia and establish robust clinical evidence. In addition, there is a need to create awareness, build the capacity of healthcare providers, and foster academic-industrial research in indigenous Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) systems.

Silymarin prevents endothelial dysfunction by upregulating Erk-5 in oxidized LDL exposed endothelial cells.

Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) has been identified as an underlying cause of ED and atherosclerosis in metabolic disorders. Silymarin (Sym), a flavonolignan, possesses various pharmacological activities however its preventive mechanism in ED warrants further investigation. Here, we have examined the effects of Sym in regulating the expression of Erk-5 and ameliorating ED using in vitro and in vivo models. Primary human umbilical vein endothelial cells (pHUVECs) viability was measured by MTT assay; mRNA and protein expression by RT-qPCR and Western blotting; tube-formation assay was performed to examine endothelialness. In in-vivo experiments, normal chow-fed mice (control) or high-fat diet (HFD)-fed mice were administered Sym or Erk-5 inhibitor (BIX02189) and body weight, blood glucose, plasma-LDL, oxLDL levels, and expression of EC markers in the aorta were examined. Sym (5 µg/ml) maintained the viability and tube-formation ability of oxLDL exposed pHUVECs. Sym increased the expression of Erk-5, vWF, and eNOS and decreased ICAM-1 at transcription and translation levels in oxLDL-exposed pHUVECs. In HFD-fed mice, Sym reduced the body weight, blood glucose, LDL-cholesterol, and oxLDL levels, and increased the levels of vWF and eNOS along with Erk-5 and decreased the level of ICAM-1 in the aorta. These data suggest that Sym could be a potent anti-atherosclerotic agent that could elevate Erk-5 level in the ECs and prevent ED caused by oxidized LDL during HFD-induced obesity in mice.

Cancer Pathways Targeted by Berberine: Role of microRNAs.

Cancer is a complex and heterogeneous malignant disease. Due to its multifactorial nature, including progressive changes in genetic, epigenetic, transcript, and protein levels, conventional therapeutics fail to save cancer patients. Evidence indicates that dysregulation of microRNA (miRNA) expression plays a crucial role in tumorigenesis, metastasis, cell proliferation, differentiation, metabolism, and signaling pathways. Moreover, miRNAs can be used as diagnostic and prognostic markers and therapeutic targets in cancer. Berberine, a naturally occurring plant alkaloid, has a wide spectrum of biological activities in different types of cancers. Inhibition of cell proliferation, metastasis, migration, invasion, and angiogenesis, as well as induction of cell cycle arrest and apoptosis in cancer cells, is reported by berberine. Recent studies suggested that berberine regulates many oncogenic and tumor suppressor miRNAs implicated in different phases of cancer. This review discussed how berberine inhibits cancer growth and propagation and regulates miRNAs in cancer cells. And how berberine-mediated miRNA regulation changes the landscape of transcripts and proteins that promote or suppress cancer progression. Overall, the underlying molecular pathways altered by berberine and miRNA influencing the tumor pathophysiology will enhance our understanding to combat the malignancy.

Synthesis and Characterization of Baicalein-loaded Aquasomes: An In vitro and In silico Perspective for Diabetes Mellitus.

BACKGROUND: Millions of individuals worldwide suffer from metabolic abnormalities induced by diabetes. Baicalein, a flavonoid, has shown several properties in various treatments with potential properties, including anti-inflammatory, antioxidant, and anti-diabetic properties. Practically, its application is hindered due to low solubility in aqueous media. Overcoming this challenge, aquasomes can offer an effective approach for delivering drugs and bioactive molecules to target various diseases. OBJECTIVE: The study aimed to develop and evaluate baicalein-loaded aquasomes for improving solubility and comparing their antidiabetic properties to acarbose through in silico docking. METHODS: Baicalein-loaded aquasomes were prepared through a three-step process: core preparation, lactose coating, and drug loading. The evaluation included assessing particle size, drug-excipient interactions, drug entrapment efficiency, loading capacity, in vitro drug release, and the kinetics of drug release. In silico docking and in vitro α-amylase inhibition activity was evaluated to assess the anti-diabetic potential of baicalein. RESULTS: The baicalein-loaded aquasomes were spherical with sizes ranging from 300-400 nm. FTIR analysis indicated no interaction between the components. The formulation exhibited drug entrapment efficiency of 94.04±0 4.01% and drug loading of 17.60 ± 01.03%. Drug release study showed sustained and complete (97.30 ± 02.06%) release, following first-order kinetics. Docking analysis revealed comparable binding affinity to acarbose, while the α-amylase inhibition assay showed greater inhibition potential of the aquasomes compared to the baicalein solution. CONCLUSION: Aquasomes offer an alternative approach to conventional delivery methods. The selfassembling characteristics of aquasomes greatly simplify their preparation process, adding to their appeal as a drug delivery system.

Diallyl Trisulfide Induces ROS-Mediated Mitotic Arrest and Apoptosis and Inhibits HNSCC Tumor Growth and Cancer Stemness.

Despite advances in therapeutic approaches, the five-year survival rate for head and neck squamous cell carcinoma (HNSCC) patients is still less than fifty percent. Research has indicated that the consumption of Allium vegetables or processed garlic containing diallyl trisulfide (DATS) can lower the risk of multiple types of cancer. Nevertheless, the effectiveness and underlying mechanisms of DATS against HNSCC have not been thoroughly explored until the current study. In this research, it was found that DATS notably curtailed the growth and viability of HNSCC cells. Additionally, DATS triggered a significant G2/M cell cycle arrest in these cells, accumulating cyclin B1, Cip1/p21, and Ser-10 phospho-histone H3-this was indicative of mitotic arrest attenuated by NAC pretreatment, suggesting the role of reactive oxygen species (ROS) induction. The production of ROS induced by DATS led to DNA damage and apoptosis, a process associated with elevated levels of cleaved caspase-3 and cleaved PARP, along with reduced XIAP. When HNSCC cells were exposed to pharmacological concentrations of DATS, it resulted in the suppression of cancer stem cell (CSC) populations, as indicated by a decrease in the CD133high/CD44high cell fraction, reduced aldehyde dehydrogenase 1 (ALDH1) activity, inhibited spheroid formation and downregulated SOX2 and Oct4 expression. Furthermore, the administration of DATS to tumor xenografts demonstrated its in vivo capacity to hinder CSCs. Further, DATS treatment inhibited the growth of UMSCC-22B head and neck cancer tumor xenograft in immunocompromised mice. Overall, DATS inhibited cell proliferation; induced cell cycle mitotic arrest and apoptosis involving DNA damage through ROS generation; reduced the CSC fraction and spheroid formation; and downregulated SOX2 and Oct4 expression. More importantly, DATS inhibited HNSCC tumor growth and CSC fraction in vivo. Thus, DATS could be a potential anticancer agent that can be used against head and neck cancer.