Evaluation of Moringa Oleifera Leaf Extract for its In vitro Antibacterial Properties, Mechanism of Action, and In vivo Corneal Ulcer Healing Effects in Rabbits' Eyes.

M. oleifera is the most adapted tree species in different medicinal eco-systems and has resilience against climate changes. This multiple-use tree provides healthy foods, snacks, honey, and fuel. Besides this, it has immense promising applicationsby offering antimicrobial and antibacterial activities for targeted uses. This validates the court of Hippocrates that let food be the medicine and medicine be the food for which moringa qualifies. In view of this, the antioxidant and in vitro antibacterial potency of the hydro-ethanolic extract of M. oleifera was evaluated on clinically isolated multidrug-resistant strains of Staphylococcus aureus. Furthermore, in vivo, the healing response of M. oleifera extract was analysed on corneal ulcers induced in rabbit eyes infected with methicillin-resistant Staphylococcus aureus. TheM. oleifera extract exhibited exponential antioxidant activity. In-vitro antibacterial activity was evaluated by agar well diffusion assay showing zone of inhibition ranging from 11.05±0.36 to 20±0.40 mm at concentrations of 20, 40, 80, and 160 mg/ml, whereas, in our finding, no zone of inhibition was observed below 20 mg/ml concentration, which indicated that there is threshold limit below which the antibacterial activity of M. oleifera extract is not observed. Furthermore, continuous application of 3% and 5% M. oleifera extract (eye drop) four times a day for 14 consecutive days showed a significant healing response of the eyes of rabbits with corneal ulcers. These results suggest that M. oleifera extract could be a viable alternative to existing antibacterial therapies for corneal ulcers. Additionally, there is a possibility of commercial formulation of M. oleifera extract in the form of deliverable pharmaceutical products; therefore, it should be explored further.

Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

The pandemic's unseen wounds: COVID-19's profound effects on mental health.

Objective: This review aims to explore the impact of the COVID-19 pandemic on mental health, with a focus on the physiological and psychological consequences, including comorbidities. The goal is to understand the direct and indirect populations affected by mental distress and identify potential interventions. Methodology: A comprehensive literature search was conducted using various databases, including Google Scholar, ResearchGate, ScienceDirect, PubMed, PLoS One, and Web of Science. The search utilized relevant keywords to investigate the direct and indirect impacts of COVID-19 on mental health. The selected articles were critically evaluated and analyzed to identify key findings and insights. Main findings: Mental health, being an intrinsic component of overall well-being, plays a vital role in physiological functioning. The COVID-19 pandemic, caused by the emergence of the novel SARS-CoV-2 virus, has had a devastating global impact. Beyond the respiratory symptoms, individuals recovering from COVID-19 commonly experience additional ailments, such as arrhythmia, depression, anxiety, and fatigue. Healthcare professionals on the frontlines face an elevated risk of mental illness. However, it is crucial to recognize that the general population also grapples with comparable levels of mental distress. Conclusion: The COVID-19 pandemic has underscored the significance of addressing mental health concerns. Various strategies can help mitigate the impact, including counselling, fostering open lines of communication, providing mental support, ensuring comprehensive patient care, and administering appropriate medications. In severe cases, treatment may involve the supplementation of essential vitamins and antidepressant therapy. By understanding the direct and indirect impacts of COVID-19 on mental health, healthcare providers and policymakers can develop targeted interventions to support individuals and communities affected by the pandemic. Continued research and collaborative efforts are essential to address this pervasive issue effectively.

Mechanistic insights of Euphorbia milii des moul mediated biocompatible and non-cytotoxic, antimicrobial nanoparticles: an answer to multidrug resistant bacteria.

The emergence of drug-resistant microbial pathogens is a matter of global concern and become more serious if they linked with healthcare-associated infections (HAIs). As per World Health Organization statistics, multidrug-resistant (MDR) bacterial pathogens account for between 7 and 12% of the worldwide burden of HAIs. The need for an effective and environmentally sustainable response to this situation is urgent. The primary goal of this study was to create copper nanoparticles that are biocompatible and non-toxic by using an extract of Euphorbia des moul, and then to test these nanoparticles' bactericidal efficacy against MDR strains of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. UV-Vis spectroscopy, dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy techniques were used to characterize the biogenic G-CuNPs. It was found that G-CuNPs were spherical in shape, with an average diameter of ~ 40 nm and a charge density of - 21.52 mV. The G-CuNPs fully eradicated the MDR strains at a dosage of 2 mg/ml with 3 h of incubation time. Mechanistic analysis showed that the G-CuNPs efficiently disrupted the cell membrane and damaged the DNA and by generating more reactive oxygen species. Moreover, cytotoxic examination revealed that G-CuNPs displayed < 5% toxicity at 2 mg/ml concentration on human RBCs, PBMCs, and A549 cell lines, suggesting that they are biocompatible. This nano-bioagent is an eco-friendly, non-cytotoxic, non-hemolytic organometallic copper nanoparticles (G-CuNPs) with a high therapeutic index for possible use in the prevention of biomedical device-borne infections by preparing an antibacterial layer on indwelling medical devices. However, its potential clinical use has to be further studied through in vivo testing with an animal model.

Novel Biocompatible Green Silver Nanoparticles Efficiently Eliminates Multidrug Resistant Nosocomial Pathogens and Mycobacterium Species.

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

Enhanced in-vitro anti-Candida efficacy of Euphorbia milii Des Moul mediated copper nanoparticles against clinically isolated Candida albicans.

Background and Purpose: Emergence of fungi as a pathogenic threat presents a significant challenge to public health, notably in intensive care units (ICUs) and among immunocompromised patients. Various factors, including sepsis-induced barrier disruptions, immune system dysfunction, and extremes of age, contribute to increased susceptibility to fungal infections. Hospital practices, such as prolonged surgeries, broad-spectrum antibiotic use, and invasive procedures, further exacerbate the risk. Fungal bloodstream infections, particularly those caused by Candida albicans, rank among the most common hospital-acquired infections, leading to substantial morbidity and mortality. The global rise in invasive candidiasis, particularly due to non-albicans Candida species, presents challenges in the diagnosis and treatment due to nonspecific symptoms and emerging antifungal resistance. Nanotechnology interventions particularly by utilizing green synthesized copper nanoparticles could possibly provide a novel solution to combat microbial colonization, biofilm formation, and drug resistance. This study aimed to assess the prevalence of candidemia, identify the distribution of causative Candida species, and understand their susceptibility patterns to commonly used antifungal agents for effective management in ICU settings. Additionally, the study sought to explore the in vitro anti-Candida activity of green copper nanoparticles synthesized using Euphorbia milii des moul extract. Materials and Methods: This study was conducted at Microbiology Laboratory of Maharishi Markandeshwar Institute of Medical Sciences and Research from January to December 2022, focused on ICU patients suspected of bloodstream infections. Blood samples were collected aseptically and processed using BD BACTECTM culture vials. Identification of organisms was performed via the Vitek-2 system by confirming candidemia with positivity in both blood samples. After that antifungal susceptibility testing was also performed against Clinical and Laboratory Standards Institute recommended antifungal drug using Vitek 2 system. G-CuNPs were synthesized using E. milii Des moul extract and possessed for physiochemical characterization. The anti-Candida activity of G-CuNPs was evaluated through the MTT assay and time kill assay. After that generation of intracellular reactive oxygen species and DNA degradation were evaluated to understand its mechanism. Results: This study identified a candidemia rate of 7.3% (58/789). Age and gender analysis revealed higher Candida colonization rates in individuals above 60 years old and females. Antifungal sensitivity profiling indicated notable resistance to fluconazole (27.59%) and voriconazole (25.86%). Synthesizing G-CuNPs using E. milii des moul extract represents a novel approach exhibiting significant fungicidal potency against clinically isolated C. albicans, supporting potential therapeutic applications. Conclusion: the findings concluded that synthesized G-CuNPs have tremendous potential to battle against medical device-borne infections by surface coating.

Prevalence of multidrug-resistant strains in device associated nosocomial infection and their in vitro killing by nanocomposites.

Background: As per WHO, global burden of healthcare-associated infections (HAIs) ranges between 7% and 12%. There is a dire need to screen Device associated nosocomial infections (DANIs) in hospitals(1). To investigate the prevalence of microbes in hospitals in DANI cases and analyse in vitro control of multi-drug resistant strains by nanotechnology intervention. Methods: Patients diagnosed with DANI were enrolled and monitored. Identification and antibiotic susceptibility pattern of the etiological agent of DANIs were made by the phenotypic method and Vitek 2 automated systems according to standard protocol. In addition, biosynthesized nanocomposite was analysed for their antimicrobial activity by agar well-diffusion method, CFU count and DNA degradation analysis. Results: There were a total of 324 patients diagnosed with DANIs. Total 369 microbial pathogens were isolated from DANI patients. The majority (87%) of the pathogenic microbes were gram-negative bacilli and all were multidrug-resistant. 41.5% of the gram-negative isolates were ESBL producers. Methicillin-resistant Staphylococcus aureus contributes about 7.3% of the total isolates in gram-positive bacteria. Nanocomposite showed 100% bactericidal activity at 5 mg/ml concentration within 3 h of incubation, whereas 2.5 mg/ml concentration of nanocomposites takes 6 h to inhibit complete growth. Conclusions: DANI, which was found in patients of all age groups, us due to multidrug-resistant gram-negative bacteria. The most commn causative agents were Acinetobacter baumannii and Citrobacter species. Nanocomposites can provide an alternative solution to prevent the DANIs.

Pattern of skin diseases among patients attending a tertiary care hospital in Lahore, Pakistan.

OBJECTIVE: There has been a rise in the magnitude of dermatological diseases in the South East Asian region. This study aimed to determine the pattern of various skin disorders appearing in the Dermatology Department of a tertiary care hospital, which will help people to understand the scale of the rising incidence and possible preventive measures that can be undertaken to curtail it. METHODS: An observational study was conducted on all the patients who attended the Dermatology Department during a one year span. A thorough medical history with detailed cutaneous examination was carried out on every patient. Investigations and skin biopsies were performed, where required, for confirmation of diagnosis. RESULTS: A total of 95,983 patients presented in the outpatient Department of Dermatology, King Edward Medical University Mayo Hospital Pakistan. Out of this sample, 24,302 patients repeatedly came to the hospital for a follow up visit related to their diseases, while 71,681 were enrolled as new cases. This group comprised 58% females and 42% males; most patients were in the 20-40 years age group. Out of 71,681, eczema was diagnosed in 22,275 (31.07%), infections including bacterial, viral, fungal, sexually transmitted infections (STIs) in 20,178 (28.16%), acne 7910 (11.03%), drug reactions 4830 (6.74%), urticaria 2910 (4.06%), and pigmentary disorders such as lichen planus, melasma and vitiligo were reported in 2739 (3.82%) cases. In addition, psoriasis was reported in 2724 (3.80%), bullous disorders in 1187 (1.66%) and connective tissue disorders in 645 (0.90%). The majority of patients presented with advanced eczema and infectious diseases. CONCLUSION: Eczema was the most common skin disease seen in our study, followed by dermatological infections. The emerging challenges for dermatologists are to prevent and reduce these skin diseases that pose a major healthcare burden, as well as affect the quality of patients' lives.

Lamellar ichthyosis with rickets.

Lamellar ichthyosis (LI) is a rare genetic disorder with autosomal recessive inheritance. It is equally seen in both sexes and usually manifests at birth. The child presents as a collodion baby. The erythema is minimal or absent; but when present, it is maximum on the face. The scaling is generalized, accentuated on lower extremities and flexural areas. Rickets is a condition in which there is softening of bones leading to fractures and deformities. It is caused by vitamin D deficiency & lack of adequate calcium in diet. Children, 6 to 24 months of age, are at a higher risk due to rapidly growing bones. The association between various types of ichthyoses and rickets is well documented. We report a case of lamellar ichthyosis with rickets in a 14-year-old girl from our part of the world.

Successful treatment of proximal white subungual onychomycosis with oral terbinafine therapy.

Proximal white subungual onychomycosis (PWSO) is a rare form of onychomycosis of both fingernails and toenails. It occurs when the fungus invades the stratum corneum of the proximal nailfold followed by infection of the deeper parts of the nail plate. The surface of the overlying nail is usually normal. A case of PWSO is described with complete cure by the use of oral terbinafine 250 mg/day for 3 months continuously.

Itraconazole pulse therapy in the treatment of disto-lateral subungual onychomycosis.

OBJECTIVE: To assess the efficacy of itraconazole pulse therapy in disto-lateral subungual onychomycosis. DESIGN: Quasi interventional study. PLACE AND DURATION OF STUDY: The study was conducted at the Department of Dermatology, KEMC/Mayo Hospital, Lahore, during the period from 1996-1998. SUBJECTS AND METHODS: Sixty-seven patients, ages ranging from 19 to 55 years, with disto-lateral subungual onychomycosis were enrolled in the study period. Therapy was started with short pulse doses of itraconazole 200 mg twice daily for one week followed by a medicine-free interval of three weeks. Pulses were administered for two consecutive months in fingernail and three months for toenail onychomycosis. Patients were followed up to six months for fingernail onychomycosis and nine months for toenail onychomycosis. RESULTS: Out of 67 cases, there were 62 evaluable patients. Trichophyton rubrum was the most common pathogen, isolated in 42 (67.8%) followed by Candida in 11 (17.8%), T. violaceum in 5 (8%), T. interdigitale in 3 (4.8%) and Epidermophyton floccosum in one (1.6%). Fingernails were affected in 46 cases whereas 16 had toenail infection. Clinical cure in finger and toenail onychomycosis was seen in 41 (89%) and 13 (81.2%) patients, respectively while mycological cure in 43 (93.5%) and 14 (87.5%) patients, respectively with itraconazole pulse therapy. CONCLUSION: Itraconazole was found to be effective, well-tolerated and safe therapy for disto-lateral subungual onychomycosis.