Delineating the Antiapoptotic Property of Apigenin as an Antitumor Agent: A Computational and In Vitro Study on HeLa Cells.

Apigenin, a flavonoid, is reported to have multiple health benefits including cancer prevention; this study evaluates the drug likeliness and Swiss ADME properties of apigenin. Apoptosis, which is a key hallmark of cancer, is associated with the deregulation of the balance between proapoptotic proteins and antiapoptotic proteins such as BCL-2,BCL-xl, BFL-1, BCL-w, BRAG-16, and MCL-1. The docking studies of apigenin with the mentioned proteins was performed to identify the interactions between the ligand and proteins, which suggested that apigenin was able to bind to most of the proteins similar to the inhibitory molecules of its native structure. A remarkable reduction in the total energy after energy minimization of apigenin-antiapoptotic protein complexes suggested increased stability of the docked complexes. The same complexes were found to be stable over a 10 ns period of molecular simulation at 300 K. These findings advocated the study to evaluate apigenin's potential to inhibit the HeLa cells at 5, 10, and 15 µM concentrations in the clonogenic assay. Apigenin inhibited the colony-forming ability of HeLa cells in a dose-dependent manner over a fortnight. Light microscopy of the treated cells displayed the morphological evidence characteristic of apoptosis in HeLa cells such as blebbing, spike formation, cytoplasmic oozing, and nuclear fragmentation. Thus, these results clearly indicate that apigenin may be used as a potential chemopreventive agent in cervical cancer management.

Smoking behaviour in post-acute myocardial infarction patients: cross-sectional study.

Introduction: Heart disease remains the leading cause of death in developed countries, and cigarette smoking contributes to a significant proportion of cardiovascular-related deaths. Abstaining from tobacco use is associated with a significant reduction in the risk of recurrent myocardial infarctions. Methodology: In this cross-sectional study, 384 participants post-acute myocardial infarction (MI) were recruited through random sampling to explore the associations between smoking status and intention to quit smoking. Data collection took place over a 6-month period at a tertiary care hospital, Islamabad, Pakistan. Results: The majority of participants were male (59.9%) and fell into the age category of 46-50 years (37.5%). Heavy daily smokers comprised the largest smoking group (41.6%), and non-ST-elevated MI was the most common subtype (40.1%). Intention to quit smoking varied among participants, with the pre-contemplation stage having the highest representation (19.3%), followed by contemplation (25.8%). Notably, a significant proportion of participants expressed no intention to quit smoking (35.4%). Conclusion: Multinomial logistic regression analysis identified current smoking as a significant predictor of intention to quit in the preparation and contemplation stages. Overall, this study underscores the importance of considering smoking behaviour when evaluating the intention to quit smoking post-MI and highlights the need for tailored interventions and support strategies to address smoking cessation in this population. These findings offer valuable insights for the development of effective strategies aimed at reducing persistent smoking following MI and improving patient outcomes.

Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology.

PURPOSE OF REVIEW: Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin-angiotensin-aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors. RECENT FINDINGS: Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation. SUMMARY: Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

Facile synthesis of substituted 2-aroylbenzo[b]thiophen-3-ols to form novel triazole hybrids using click chemistry.

An efficient one-pot method is proposed for the synthesis of 2-aroylbenzo[b]thiophen-3-ols from 2-mercaptobenzoic acid and various substituted aryl bromomethyl ketones in the presence of triethylamine. The reaction is likely to proceed through SN2-type nucleophilic attack of the sulfhydryl group in thiosalicylic acid on bromomethyl ketone in the presence of a base to afford sulfanylbenzoic acid, which undergoes an intramolecular cyclization in situ to furnish 2-aroylbenzo[b]thiophen-3-ol in high yield. To investigate the utility of the synthesized benzothiophene scaffold, an alkyne moiety was introduced at the 3-hydroxy position and subsequently subjected to a click reaction to form novel benzothiophene-triazole hybrids in good yields. A simple and straightforward approach to synthesizing 2-aroylbenzo[b]thiophen-3-ols can open new avenues for discovering novel biological and pharmaceutical compounds.

Corneal Neurotization: Essentials for The Facial Paralysis Surgeon.

Deficits in corneal innervation lead to neurotrophic keratopathy (NK). NK is frequently associated with facial palsy, and corneal damage can be accelerated by facial palsy deficits. Corneal nerves are important regulators of limbal stem cells, which play a critical role in epithelial maintenance and healing. Nonsurgical treatments of NK have undergone recent innovation, and growth factors implicated in corneal epithelial renewal are a promising therapeutic avenue. However, surgical intervention with corneal neurotization (CN) remains the only definitive treatment of NK. CN involves the transfer of unaffected sensory donor nerve branches to the affected cornea, and a variety of donor nerves and approaches have been described. CN can be performed in a direct or indirect manner; employ the supraorbital, supratrochlear, infraorbital, or great auricular nerves; and utilize autograft, allograft, or nerve transfer alone. Unfortunately, comparative studies of these factors are limited due to the procedure's novelty and varied recovery timelines after CN. Regardless of the chosen approach, CN has been shown to be a safe and effective procedure to restore corneal sensation and improve visual acuity in patients with NK.

Acute kidney injury in birth asphyxiated patients: A cross sectional study at Bahawal Victoria Hospital.

BACKGROUND: The presence of perinatal asphyxia and its severity appear to correlate with increasing incidence of Acute kidney injury (AKI). The objective of this study is to determine the frequency of AKI and its outcome in birth asphyxia. METHODS: This cross-sectional study was carried out in the Department of Pediatric Medicine from March 2019 to September 2019. A total of 111 newborns with birth asphyxia of gestational age 37-41 weeks were included. Neonates born to mothers having hypertension and diabetes mellitus, patients with congenital kidney anomalies like polycystic kidney disease and renal agenesis, and mothers taking nephrotoxic drugs or any other known cause of AKI like hypovolemic shock were excluded. Urine output (UOP) and final outcome of the patient were also noted. AKI was noted. RESULTS: The mean gestational age was 38.29 ± 1.07 weeks. The mean weight of neonates was 3.08 ± 0.31 kg. The frequency of AKI in birth asphyxia was 20 (18.02%) neonates. Complete recovery in AKI patients was seen in 07 (35.0%) and death in 13 (65.0%) patients. CONCLUSION: This study has shown that the frequency of AKI in birth asphyxia was found in 18.02% neonates with complete recovery seen in 35.0% and death in 65.0% patients.

Gender differences in the surgical management of trachomatous trichiasis: an exploratory analysis of global trachoma survey data, 2015-2019.

BACKGROUND: Trachomatous trichiasis (TT) is a painful, potentially blinding eye condition that can be managed through epilation or surgery. Women are affected by TT approximately twice as often as men and are believed to face gendered barriers to receiving surgical care to prevent vision loss. METHODS: We used data from 817 cross-sectional surveys conducted during 2015-2019 in 20 African countries to estimate the prevalence difference (PD) between female and male eyes for four outcomes potentially indicating gender-related differences in TT management: (1) received surgery and developed postoperative TT (PTT), (2) never offered surgery, (3) offered surgery but declined it, and (4) offered epilation but never offered surgery. RESULTS: The prevalence was modestly elevated among female eyes compared with male eyes for having PTT (PD:1.8 [95% confidence limits (CL): 0.6, 3.0]) and having declined surgery for the eye (PD: 6.2 [95% CL: 1.8, 10.7]). The proportion offered epilation was similar by gender (PD:0.5 [95% CL: -0.4, 1.3]), while never having been offered surgery was somewhat more prevalent among male eyes (PD: -2.1 [95% CL: -3.5, -0.7]). CONCLUSIONS: Our results suggest potential gender differences in TT management. More research is needed to determine the causes and implications of the observed differences.

Co-administration of Chrysin and Luteolin with Cisplatin and Topotecan Exhibits a Variable Therapeutic Value in Human Cancer Cells, HeLa.

Combinational treatment is a promising strategy for better cancer treatment outcomes. Chrysin and luteolin have demonstrated effective anticancer activity. Cisplatin and topotecan are commonly used for the treatment of human cancers. However, various side effects including drug resistance are an imperative restriction to use them as pharmacological therapy. Therefore, the aim was to use these agents in combination with flavones for better efficacy. In the present study, it was found that the combination of chrysin and cisplatin and luteolin and cisplatin significantly improved the anticancer effect as both the combinations showed synergistic interactions [combinational index (CI < 1)]. Remarkably, the combination of chrysin and luteolin with topotecan depicted the antagonistic interaction (CI > 1). Further, increased expression of the pro-apoptotic proteins Bax and caspase 8 and the inhibition of the antiapoptotic protein Bcl-2 were instituted in the synergistic doses (chrysin + cisplatin and luteolin + cisplatin), hence promoting apoptosis. Also, it was found that the synergistic combination inhibited the migration of HeLa cells by downregulation of metalloproteases and upregulation of TIMPs. However, there are no significant changes depicted in the antagonistic combinations which support their role in their antagonistic effects. Based on these results, it can be inferred that the two or more drug combinations need to be explored well for their interaction to enhance the therapeutic outcomes.

Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models.

BACKGROUND: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. PURPOSE: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. METHODS: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. CONCLUSION: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.

Prospects of earthworm coelomic fluid as a potential therapeutic agent to treat cancer.

Cancer is a major public health concern because it is one of the main causes of morbidity and mortality worldwide. As a result, numerous studies have reported the development of new therapeutic compounds with the aim of selectively treating cancer while having little negative influence on healthy cells. In this context, earthworm coelomic fluid has been acknowledged as a rich source of several bioactive substances that may exhibit promising anticancer activity. Therefore, the objective of the present review is to evaluate the findings of the reported studies exploring the antitumor effects of coelomic fluid in the context of its possible utilization as a natural therapeutic agent to cure different types of cancer. The possible mechanisms underlying the coelomic fluid's anticancerous potential as well as the possibility for future development of cutting-edge therapeutic agents utilizing coelomic fluid-derived natural bioactive compounds to treat cancer disorders have been discussed along with future challenges. In addition, the feasibility of encapsulation of bioactive compounds derived from coelomic fluid with nanomaterials that could be further explored to attain more effective anticancer competence is discussed.

Metagenomic investigations on antibiotic resistance and microbial virulence in oil-polluted soils from China.

Engine oil spills have been associated with a wide range of human health problems. However, little is known about the effects of petroleum hydrocarbon pollution on soil microbial communities. In this study, three samples were collected from oil-polluted soils (OPS), and one control soil (CS) from Taolin town, China, near the old engine's scrapes was used. The aims of this study were to conduct metagenomic sequencing and subsequently perform resistome and virulome analysis. We also aimed to validate anti-microbial resistance and virulence genes and anti-bacterial sensitivity profiles among the isolates from oil-polluted soils. The OPS microbial community was dominated by bacterial species compared to the control samples which were dominated by metazoans and other organisms. Secondly, the resistosome and virulome analysis showed that ARGs and virulence factors were higher among OPS microbial communities. Antibiotic susceptibility assay and qPCR analysis for ARGs and virulence factors showed that the oil-polluted soil samples had remarkably enhanced expression of these ARGs and some virulence genes. Our study suggests that oil pollution contributes to shifting microbial communities to more resilient types that could survive the toxicity of oil pollution and subsequently become more resilient in terms of higher resistance and virulence potential.

Successful utilization of nirmatrelvir/ritonavir and dexamethasone in a patient with total artificial heart and COVID-19: A case report.

RATIONALE: Management of coronavirus disease 2019 (COVID-19) has been the subject of extensive research and study, leading to the development of strategies and treatments. Nonetheless, there remains a dearth of information concerning patients who require mechanical circulatory system support. This case report presents one of the first documented cases of successful utilization of nirmatrelvir/ritonavir (Paxlovid) and dexamethasone in the treatment of a patient with a total artificial heart. PATIENT CONCERNS: The patient in this case study was a 28-year-old male who had been experiencing severe heart failure. In need of a heart transplant, he underwent a procedure for implantation of a total artificial heart as a bridge to transplantation. DIAGNOSES: Unfortunately, after the surgical intervention, the patient contracted COVID-19, as confirmed by polymerase chain reaction. INTERVENTIONS: The therapeutic approach involved a 5-day regimen of nirmatrelvir/ritonavir at a dosage of 300/100 mg administered twice daily, along with a daily dosage of 6 mg of dexamethasone. OUTCOMES: Remarkably, the patient oxygenation level improved on the second day of therapy. Consequently, he was transferred from the intensive care unit to the general floor. After 71 days with the total artificial heart, the patient successfully underwent heart transplantation. LESSONS: This case report provides a compelling example of the successful application of nirmatrelvir/ritonavir and dexamethasone in the treatment of a COVID-19 patient with a total artificial heart. The positive outcome observed in this case underscores the potential use of these therapeutic agents in this specific patient population. However, it is imperative to conduct further research to corroborate and validate these initial findings. This study lays the foundation for further exploration of the efficacy of these drugs in patients with mechanical circulatory support systems.

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review.

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.

Pattern of dyslipidemia and associated factors in coronary artery disease patients in Khyber Pakhtunkhwa: A cross-sectional secondary data analysis.

Objectives: To assess the prevalence, pattern, and associated factors of dyslipidemia in patients with coronary artery disease (CAD) in the Northwest region of Pakistan. Method: A cross-sectional secondary data analysis was performed on CAD patients visiting cardiology clinics in selected hospitals from July to December 2019. A total of 362 patients were included via consecutive sampling. Dyslipidemia was operationalized according to the "National Cholesterol Education Program (NCEP ATP III) guidelines". Results: Mixed dyslipidemia was recorded in 92.26% of the patients, while isolated dyslipidemia was observed in 5.24%. A high prevalence of combined dyslipidemia with increased LDL-C, TG, and low HDL-C was noted. Contrarily, elevated LDL-C was the commonest single lipid disorder (84.25%). Hypercholesterolemia was the least common disorder. Increasing BMI was found to be independently associated with hypercholesterolemia (OR: 1.19). Similarly, age (OR: 0.97) and being a rural resident (OR: 2.61) were independent factors associated with hypertriglyceridemia. Furthermore, being an urban resident (OR: 2.25) and increasing BMI (OR: 1.77) were also significantly associated with high LDL-C. Conclusion: Mixed dyslipidemias were observed in the majority of the patients. Age, BMI, and residence were noted to be independently associated with abnormal lipids. Early screening and proper management should be encouraged to minimize this significant cardiovascular risk.

The Role of Sensory Innervation in Homeostatic and Injury-Induced Corneal Epithelial Renewal.

The cornea is the window through which we see the world. Corneal clarity is required for vision, and blindness occurs when the cornea becomes opaque. The cornea is covered by unique transparent epithelial cells that serve as an outermost cellular barrier bordering between the cornea and the external environment. Corneal sensory nerves protect the cornea from injury by triggering tearing and blink reflexes, and are also thought to regulate corneal epithelial renewal via unknown mechanism(s). When protective corneal sensory innervation is absent due to infection, trauma, intracranial tumors, surgery, or congenital causes, permanent blindness results from repetitive epithelial microtraumas and failure to heal. The condition is termed neurotrophic keratopathy (NK), with an incidence of 5:10,000 people worldwide. In this report, we review the currently available therapeutic solutions for NK and discuss the progress in our understanding of how the sensory nerves induce corneal epithelial renewal.

Genomic and functional portrait of multidrug-resistant, hydrogen sulfide (H2S)-producing variants of Escherichia coli.

Atypical Escherichia coli forms exhibit unusual characteristics compared to typical strains. The H2S-producing variants of some atypical E. coli strains cause a wide range of illnesses in humans and animals. However, there are sparse reports on such strains worldwide. We performed whole-genome sequencing (WGS) and detailed characterization of four H2S-producing E. coli variants from poultry and human clinical sources in Dhaka, Bangladesh. All four isolates were confirmed as E. coli using biochemical tests and genomic analysis, and were multidrug-resistant (MDR). WGS analysis including an additional Chinese strain, revealed diverse STs among the five H2S-producing E. coli genomes, with clonal complex ST10 being detected in 2 out of 5 genomes. The predominant phylogroup detected was group A (n = 4/5). The blaTEM1B (n = 5/5) was the most predominant extended-spectrum beta-lactamase (ESBL) gene, followed by different alleles of blaCTX-M (blaCTX-M -55,-65,-123; n = 3/5). Multiple plasmid replicons were detected, with IncX being the most common. One E. coli strain was classified as enteropathogenic E. coli. The genomes of all five isolates harbored five primary and four secondary function genes related to H2S production. These findings suggest the potential of these isolates to cause disease and spread antibiotic resistance. Therefore, such atypical E. coli forms should be included in differential diagnosis to understand the pathogenicity, antimicrobial resistance and evolution of H2S-producing E. coli.

Case report: A successfully treated case of community-acquired urinary tract infection due to Klebsiella aerogenes in Bangladesh.

Klebsiella aerogenes, a nosocomial pathogen, is increasingly associated with extensive drug resistance and virulence profiles. It is responsible for high morbidity and mortality. This report describes the first successfully treated case of community-acquired urinary tract infection (UTI) caused by Klebsiella aerogenes in an elderly housewife with Type-2 diabetes (T2D) from Dhaka, Bangladesh. The patient was empirically treated with intravenous ceftriaxone (500 mg/8 h). However, she did not respond to the treatment. The urine culture and sensitivity tests, coupled with bacterial whole-genome sequencing (WGS) and analysis, revealed the bacteria to be K. aerogenes which was extensively drug-resistant but was susceptible to carbapenems and polymyxins. Based on these findings, meropenem (500 mg/8 h) was administered to the patient, who then responded to the treatment and recovered successfully without having a relapse. This case raises awareness of the importance of diagnosis of not-so-common etiological agents, correct identification of the pathogens, and targeted antibiotic therapy. In conclusion, correctly identifying etiological agents of UTI using WGS approaches that are otherwise difficult to diagnose could help improve the identification of infectious agents and improve the management of infectious diseases.

Current status of cardiopulmonary resuscitation training and automatic external defibrillator availability in high schools in Halifax, Nova Scotia, Canada.

Background: School-based cardiopulmonary resuscitation (CPR) training and early use of an automated external defibrillator (AED) have proven to increase the survival of victims of sudden cardiac arrest (SCA). This study aimed to determine the status of CPR training, availability of AEDs, and medical emergency response programs (MERPs) in high schools in Halifax Regional Municipality. Method: High school principals were asked to participate in a voluntary online survey comprising questions about demographics, AEDs availability, CPR training for staff and students, the existence of MERPs, and perceived barriers. Three autogenerated reminders followed the initial invitation. Results: Out of 51 schools, 21 (41%) responded, only 10% (2/21) and 33% (7/21) reported providing CPR training to students and staff, respectively. About 35% (7/20) of the schools reported having AEDs, but only 10% (2/20) have MERPs for SCA. All respondents reported in favor of AED availability in schools. The reported barriers to CPR training included limited financial resources (54%), perception of low priority (23%), and time constraints (23%). Respondents reported limited financial resources (85%) and the lack of trained staff to use (30%) as the main reasons for the unavailability of AEDs. Conclusion: This survey showed that all respondents overwhelmingly favour having access to AEDs. However, the availability of CPR and AED training for staff and students in schools remains inadequate. Emergency action plans have not been devised, and few schools have AED devices. More education and awareness are needed to ensure lifesaving equipment and practices in all Halifax Regional Municipality schools.