Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure-activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

Evaluation of Anesthetic Efficacy of 4% Articaine, 0.5% Bupivacaine and 0.5% Ropivacaine During Surgical Removal of Impacted Mandibular Third Molars: A Randomized Comparative Clinical Study.

Introduction: The aim of this study was to compare the anesthetic efficacy of 4% articaine, 0.5% bupivacaine and 0.5% ropivacaine (with 1:200,000 adrenaline) during surgical removal of impacted mandibular third molars. Materials and methods: The study included 75 patients randomly divided into three equal groups of 25 patients each. The study variables were: onset of anesthetic action, duration of surgery and anesthesia and postoperative analgesia. A visual analog scale was used to assess pain at different time intervals. Statistical analysis revealed insignificant difference among groups in terms of volume of anesthetic solution used, quality of anesthesia, surgical difficulty and duration of surgery. Results: The mean onset time was significantly (P < 0.001) shorter for articaine (1.14 min) than ropivacaine (2.18 min) and bupivacaine (2.33 min). However, the duration of anesthesia as well as analgesia was significantly (P < 0.001) longer for bupivacaine (483.6 min and 464 min) and ropivacaine (426.6 min and 459 min) as compared to articaine (232.8 min and 191.4 min), respectively. Also, on comparing three groups pain scores at 6th postoperative hour were significant (P < 0.01). Conclusion: Ropivacaine and bupivacaine can be safely used in patients where longer duration of surgery is anticipated.

Green and efficient extraction of phenolic compounds from Neem leaves using deep eutectic solvents based ultrasonic-assisted extraction.

Deep eutectic solvent (DES) combined with ultrasonic-assisted extraction was employed as an environmentally friendly technique for extracting antioxidant phenolic compounds from Neem leaves in place of organic solvents. Choline chloride-Ethylene glycol (1:2) with 40% V/V water content (DES-1) was investigated as a potential total phenolic content extractant (38.2 ± 1.2 mg GAE/g DW, where GAE: gallic acid equivalent, DW: dry weight). The optimal operational parameters assessed using single-factor experiments to maximize the total phenolic compounds content were as follows: extraction time of 30 min, 40% V/V water content, liquid-solid ratio of 15:1, and room temperature. Additionally, the in-vitro antioxidant experiments (2,2-diphenyl-1- picrylhydrazyl radical scavenging assay and ferric reducing antioxidant power assay) demonstrated the DES-1-based extract of Neem leaves as a potent antioxidant agent, compared to traditional solvents. Moreover, microscopic morphological analysis supported the effectiveness of DES-1 for the noticeable alteration in the fiber surface structure of Neem leaves after extraction which benefited in the release of polyphenols from these leaves. Eventually, the mass analysis of the extract disclosed the presence of eleven polyphenols in the extract. The Green Analytical Procedure Index revealed the greenness of the extraction method.

Current Concepts and Recent Updates of Optical Biometry- A Comprehensive Review.

One of the most recent advancements in the field of cataract surgery is optical biometry. With the advent of optical biometry ocular measurements are now simpler, quicker, and more precise. The devices have made intraocular lens (IOL) power calculations easier in difficult situations too, such as in cases with extremes of axial lengths, silicone filled eyes, cataract surgery in post-keratoplasty eyes, post Laser-Assisted in Situ Keratomileusis (LASIK) eyes, etc. The gold standard for IOL power calculation in the present day is by the use of optical biometry devices. The anatomical measurements by these devices are highly precise and because of these measurements and the incorporation of various IOL power calculation formulas the optical biometry devices give the accurate power and the post-operative visual outcome is highly satisfactory among the patients. The growing use of these devices has made cataract the most commonly performed refractive surgical procedure nowadays. In the current scenario, optical biometry has widespread acceptance in almost all countries and has many advantages over ultrasound or immersion biometry. Cataract surgeons can obtain easy and reliable measurements from these devices. Refractive surprises have also decreased considerably with their use. This article will comprehensively review the principles of the various optical biometry devices, the parameters used in each of the devices, the advantages and disadvantages, and add more like what all this article will add.

Exploring the broad-spectrum pharmacological activity of two less studied Australian native fruits: chemical characterisation using LCMS-driven metabolomics.

Australian fruits such as native currant (Acrotriche depressa) and lemon aspen (Acronychia acidula) are under-examined in terms of their therapeutic potential. In this study, the in vitro antiproliferative activity of native currant and lemon aspen extracts (water and ethanol) against MCF7 breast adenocarcinoma cells was determined using the Alamar blue assay. The most potent extracts (native currant water, NC-W; native currant ethanol, NC-Et; lemon aspen ethanol, LA-Et) were further evaluated using flow cytometry to detect the potential induction of apoptosis in MCF7 cells whereas 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was implemented to understand the impact of the extracts on the intracellular reactive oxygen species (ROS) levels in MCF7 cells. Furthermore, the antioxidant activity of the extracts was assessed using ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate)], and CUPRAC (cupric reducing antioxidant capacity) assays. The antimicrobial susceptibility testing of NC-W, NC-Et, and LA-Et was carried out against Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and yeast (Candida albicans) strains using a resazurin-based assay. Additionally, potential metabolites in the NC-W and NC-Et extracts were analysed with liquid chromatography-mass spectrometry (LC-MS) driven metabolomics and chemometrics to spot differential and major metabolites. A dose-dependent antiproliferative activity was conferred by the NC extracts against MCF7 cells. Of the two LA extracts, only LA-Et showed a dose-dependent antiproliferative activity at higher concentrations. Both NC extracts and LA-Et induced apoptosis in MCF7 cells. None of the extracts increased the production of ROS significantly in MCF7 cells compared to the untreated control. A dose-dependent antioxidant activity was observed in both antioxidant assays. Both NC and LA extracts showed a similar minimum inhibitory concentration (MIC) value against S. aureus. Only LA-Et showed activity against E. coli, while NC-W and NC-Et were less active. All extracts showed MIC values of >1500 µg mL-1 against C. albicans. The metabolomics analysis revealed an abundance of flavonoids, fatty acyl derivatives, carbohydrates, carboxylic acids and their derivatives, and alkaloid compounds as potential bioactive metabolites in the NC extracts. In conclusion, both NC and LA showed antiproliferative (against MCF7 breast adenocarcinoma cells through the induction of apoptosis), strong antioxidant and minimal antimicrobial properties.

Use of Artificial Intelligence Tools for Research by Medical Students: A Narrative Review.

With the advent of the era of digitalization, a new door has opened for the development of artificial intelligence (AI)-driven tools/algorithms that can help analyse the huge amount of data uploaded onto the cloud. AI-based tools/algorithms have created a niche in the field of research. AI has enabled researchers and practitioners to access and evaluate an enormous number of scientific papers more effectively. This can link similar studies from the past and highlight research gaps, thus accelerating the literature review, evidence generation, and knowledge discovery process. Medical students can obtain help from various AI-based solutions for literature organization and citations. These tools/algorithms facilitate secure information exchange, collaborative research efforts, and communication among multiple research centres. However, AI-driven research requires the guidance and supervision of human experts for better accuracy, coherence, and credibility of the content entering scientific databases. The key objective of this review is to discuss and evaluate various AI-based tools/algorithms and their key features that can assist medical students in medical research.

Facile Layer Diffusion Technique for Synthesis of Terbium-Based Metal Organic Framework for Fluorometric Sensing of Hydroquinone.

A photoluminescent terbium (III)-based Metal Organic Framework (MOF) was synthesized at room temperature by layer diffusion method utilizing mixed carboxylate linkers (4,4'-oxybis(benzoic acid) and benzene-1,3,5 tricarboxylic acid). Synthesized MOF has crystalline nature and rod-shaped morphology and is thermally stable up to 455 °C. The fluorescence emission spectra and theoretical results revealed that carboxylate linkers functioned as sensitizers for Tb(III) photoluminescence which resulted in four distinct emission peaks at 495, 547, 584, and 621 nm corresponding to the transitions 5D4 → 7F6, 5D4 → 7F5, 5D4 → 7F4, and 5D4 → 7F3. Using synthesized MOF as fluorescent probe, hydroquinone was detected in aqueous medium with a detection limit of 0.048 µM, remarkable recovery (95.6-101.1%), and relative standard deviation less than 2.25%. The quenching phenomenon may be ascribed to electron transfer from synthesized probe to oxidized hydroquinone via carboxylic groups on the surface of MOF, which is further supported by photo-induced electron transfer mechanism. This study introduces a cheaper, faster, and more accurate method for hydroquinone detection.

Navigating diagnostic and therapeutic challenges in ocular manifestations of Hansen's disease and trachoma: A narrative review.

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae , has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.

Breaking-Down Barriers: Proposal of Using Cellulose Biosynthesis Inhibitors and Cellulase Enzyme as a Novel Treatment Modality for Vision Threatening Pythium Insidiosum Keratitis.

Pythium insidiosum, an Oomycete, causes severe keratitis that endangers vision. Its clinical, morphological, and microbiological characteristics are often indistinguishable from those of fungal keratitis, earning it the moniker "parafungus". Distinctive clinical hallmarks that set it apart from other forms of keratitis include radial keratoneuritis, tentacles, marginal infiltration, and a propensity for rapid limbal spread. The therapeutic approach to Pythium keratitis (PK) has long been a subject of debate, and topical and systemic antifungals and antibacterials have been tried with limited success. Approximately 80% of these eyes undergo therapeutic keratoplasty to salvage the eye. Hence, there is a need to innovate for alternative and better medical therapy to safeguard these eyes. The resistance of Pythium to standard antifungal treatments can be attributed to the absence of ergosterol in its cell wall. Cell walls of plants and algae have cellulose as an essential constituent. Cellulose imparts strength and structure and acts as the "skeleton" of the plant. Fungal and animal cell walls typically lack cellulose. The cellular architecture of Pythium shares a similarity with plant and algal cells through the incorporation of cellulose within its cell wall structure. Inhibitors targeting cellulose biosynthesis (CBI), such as Indaziflam, Isoxaben, and Quinoxyphen, serve as critical tools for elucidating the pathways of cellulose synthesis. Furthermore, the enzymatic action of cellulase is instrumental for the extraction of proteins and DNA. To circumvent this issue, we hypothesize that CBI's and cellulase enzymes can act on the Pythium cell wall and may effectively treat PK. The available literature supporting the hypothesis and proof of concept has also been discussed. We have also discussed these drugs' molecular mechanism of action on the Pythium cell wall. We also aim to propose how these drugs can be procured and used as a potential medical management option for this devastating entity.

Pediatric corneal transplantation: techniques, challenges, and outcomes.

Pediatric corneal transplant is a highly demanding and technically challenging procedure for the cornea surgeon in today's era. These cases pose unique challenges in clinical and surgical management. The indications of pediatric corneal transplant can be therapeutic, tectonic, optical, and cosmetic. Pediatric patients undergoing corneal transplants are at a high risk of graft infection, failure, rejection, dehiscence, and amblyopia due to young age, robust immune system, increased incidence of trauma, and compliance issues. The other factors contributing to graft failure can be allograft rejection, secondary glaucoma, corneal vascularization, multiple surgeries, vitreous prolapse, and lack of treatment compliance. A successful corneal transplant in children depends on meticulous preoperative evaluation, uneventful surgery, the expertise of a corneal surgeon, and regular and timely postoperative follow-up. Therapeutic and optical penetrating keratoplasty are the most commonly performed transplants in children. However, with the advancements in surgical technique and management protocol, the current focus has shifted toward lamellar keratoplasty. Lamellar keratoplasty offers early visual recovery and potentially fewer complications. Visual rehabilitation through corneal transplant in otherwise blind eyes can be a boon for the children. Recently, keratoprostheses have been promising in children with multiple graft failures. The current review gives insights into epidemiology, etiology, indications, clinical characteristics, investigations, management options, recent advances, and the future of pediatric corneal transplants. As surgical techniques continue to grow and comprehension of pediatric corneal transplants is improving, we can safeguard these eyes with the best possible anatomical and functional outcomes.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

Bakuchiol nanoemulsion loaded electrospun nanofibers for the treatment of burn wounds.

The present work aims to develop and evaluate the wound healing potential of bakuchiol nanoemulsion loaded electrospun scaffolds. Since oxidative stress and microbial burden leads the burn wounds to become chronic and fatal to patients, a phytoconstituent, bakuchiol (BAK), was screened on the basis of antioxidant and antimicrobial potential which also defined its dose. Furthermore, BAK was incorporated into a nanoemulsion to enhance its therapeutic efficacy, reduce its dosage frequency, and maximize its stability. The present study is inclined towards the collaborative interaction of natural products and novel drug delivery systems to develop safe and therapeutically efficient systems for burn wound healing. The optimized nanoemulsion showed excellent antioxidant and antimicrobial potential against wound susceptible pathogens, i.e., Candida albicans and Methicillin-resistant Staphylococcus aureus which was further loaded into gelatin based hydrogel and nanofibrous scaffold system. The mesh structure of scaffolds was chosen as a suitable carrier system for wound healing process not only because it offers resemblance to skin's anatomy but is also capable of providing uniform distribution of wound biomarkers across the skin. The prepared nanofibers were assessed for their analgesic, anti-inflammatory, and wound healing potential which was observed to be significantly better than its gel formulation.

The Role of Serum Matrix Metalloproteinase-9 as a Predictor of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is one of the major causes of a poor neurological outcome following aneurysmal subarachnoid hemorrhage (aSAH). Several biomarkers, including matrix metalloproteinase-9 (MMP-9), have been evaluated to predict the development of DCI for timely management. This prospective cohort study was done on 98 patients with aSAH presenting within 72 h of the ictus. Serum samples were collected preoperatively, 7 days after ictus, 10 days after ictus, or when the patient developed DCI, whichever was earlier. The primary objective was to correlate the serum MMP-9 levels with the development of DCI. The secondary objectives were to correlate the serum MMP-9 levels with sonographic vasospasm and the neurological outcome. There was no correlation between the serum MMP-9 levels and the development of DCI (p = 0.37). Similarly, there was no correlation between the serum MMP-9 levels and the sonographic vasospasm (0.05) nor with the modified Rankin Scale (mRS) at discharge (p = 0.27), mRS at 3 months (p = 0.22), and Glasgow Outcome Scale Extended (GOSE) at 3 months (p = 0.15). Serum MMP-9 levels do not predict the development of DCI following aSAH.

Effectiveness of CBT for reducing depression and anxiety in people with epilepsy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with epilepsy suffer from depression and anxiety that reduces quality of life. Cognitive behavioral therapy (CBT) among various non pharmacological treatment recommended for depression and anxiety. Since there are several articles reporting CBT treatment for depression in patients with epilepsy, we conduct a meta-analysis to evaluate the effectiveness of CBT for adult patients with epilepsy. METHODS: Four electronic databases PubMed, Scopus, Embase, and the Cochrane library searched for relevant studies. A detailed "RISK of bias" assessment has been done for included studies. Funnel plot was used for assessing publication Bias. R Software- RStudio 2022 was used to calculate standard mean difference (SMD). The study has been registered in PROSPERO (CRD42023447655). RESULTS: Eventually, a Total 13 studies involving 1222 patients met the eligibility criteria. There was decline in the Patient Health Questionnaire (PHQ) [SMD = -0.42, 95 % CI = -0.63 to -0.22], Neurologic Disorder Depression Inventory-Epilepsy (NDDI-E) [SMD = -0.53, 95 % CI = -0.75 to -0.31], Beck depression Inventory (BDI) [SMD = -0.69, 95 % CI = -1.08 to -0.30], Hospital Anxiety and Depression Scale-Depression (HADS-D) [SMD = -0.73 , 95 % CI = -0.94 to -0.52] and Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) [SMD = -0.66, 95 % CI = -0.87 to -0.45] score of the CBT group than that of the control group at post-intervention. The results showed that the improvement in QOLIE-31 score of the CBT group than that of the control group [SMD = 0.67, 95 % CI = 1.33] at post-intervention. CONCLUSION: The result of our study showed that Cognitive behavioral therapy is a superior therapy for treating anxiety and depression in epilepsy patients. CBT was effective in improving Quality of life in patients with epilepsy. However, the sample size varied across the trials, additional high-quality studies are needed in the future.

The development of thymol-isatin hybrids as broad-spectrum antibacterial agents with potent anti-MRSA activity.

Bacterial resistance toward available therapeutic agents has become a nightmare for the healthcare system, causing significant mortality as well as prolonged hospitalization, thereby needing the urgent attention of research groups working on antimicrobial drug development worldwide. Molecular hybridization is a well-established tool for developing multifunctional compounds to tackle drug resistance. Inspired by the antibacterial profiles of isatin and thymol, along with the efficiency of a triazole linker in molecular hybridization, herein, we report the design, synthesis and antibacterial activity of a novel series of triazole tethered thymol-isatin hybrids. Most of the hybrids exhibited a broad-spectrum antibacterial efficacy against standard human pathogenic as well as clinically isolated multidrug-resistant bacterial strains listed in the WHO's 'priority pathogen' list and also in the ESKAPE group. Among them, hybrid compound AS8 was the most effective against methicillin-resistant Staphylococcus aureus (MIC = 1.9 µM and MBC = 3.9 µM), exhibiting biofilm inhibitory potential. AS8 exhibited dehydrosqualene synthase (CrtM) inhibitory potential in MRSA and decreased the production of virulence factor staphyloxanthin, which is one of the key mechanisms of its anti-MRSA efficacy, which was further supported by molecular docking and simulation studies. Moreover, AS8 was found to be non-toxic and showed a potent in vivo antibacterial efficacy (90% survival at 10 mg kg-1) as well as a modulated immune response in the larva-based (Galleria mellonella) model of systemic infections. Overall findings confirmed that AS8 can be a promising candidate or take the lead in the treatment and further drug development against drug-resistant infectious diseases, especially against MRSA infections.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.