Understanding the determinants of anemia reduction among women of reproductive age: Exemplar country case studies' methodology.

BACKGROUND: Since 2000, only a few countries have substantially reduced the burden of anemia among women 15-49 y of age. The Exemplars in Anemia Reduction among Women of Reproductive Age (WRA) studied the determinants of success among these countries. OBJECTIVES: To describe the methodology used to determine the factors associated with anemia reduction in high-performing countries, with the aim to guide policy and programmatic decisions in other countries with similar sociodemographic and health indices. METHODS: This article describes the process used to identify countries with exemplary reduction in WRA anemia burden, compared with their peers. We describe the Exemplars in Global Health methodology, the mixed-methods approach used to identify and quantify the macro- and microlevel characteristics associated with anemia burden decline among WRA. Quantitative analyses include descriptive and equity analyses, multivariate linear regression, and Oaxaca-Blinder decomposition analysis. Qualitative analyses include in-depth interviews and focus group discussions with national, subnational, and community stakeholders, as well as review of programs and policies with the potential to impact women's health and/or nutrition, enacted in the countries over the last 20 y. A technical advisory group oversaw all research activities. RESULTS: We identified 5 countries, namely, Mexico, Pakistan, Philippines, Uganda, and Senegal, as anemia exemplars, after considering the magnitude of anemia decline between 2000 and 2018, availability of ≥2 nationally representative anemia surveys, geographical diversity to account for the complex etiology of anemia, regional representation, and logistics of in-country work. CONCLUSIONS: Exemplars in Anemia Reduction among WRA seeks to create awareness of how little anemia prevalence has changed globally and aims to inform and spur global efforts for improving women's health and nutrition.

Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies.

BACKGROUND: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis. METHODS: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5. CONCLUSIONS: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.

Proximal tubular dysfunction as a predictor of AKI in Hospitalized COVID-19 patients.

BACKGROUND: High concentration of Angiotensin converting enzyme receptors in the proximal tubules make kidneys an early target in COVID-19. Proximal tubular dysfunction (PTD) may act as an early predictor of acute kidney injury (AKI) and more severe disease. METHODS: This prospective observational study was conducted in the COVID unit, Bangabandhu Sheikh Mujib Medical University. 87 COVID-19 patients without known kidney disease were screened for 6 markers of PTD on admission-hyperuricosuria, normoglycemic glycosuria, proteinuria, renal phosphate leak, sodium leak and potassium leak. Positivity of 2 of the first 4 markers was considered as PTD. 35 patients with PTD and 35 without PTD were followed up throughout their hospital stay. RESULTS: 52.9% had PTD on admission. The most prevalent markers were renal sodium leak (67%), followed by proteinuria (66.7%), hyperuricosuria (42.5%), potassium leak (32.2%), phosphate leak (28.7%) and normoglycemic glycosuria (20.7%). Mean age was 55.7 years. 32.9% patients developed AKI. PTD group had higher odds of developing AKI (odds ratio 17.5 for stage 1, 24.8 for stage 2 and 25.5 for stage 3; p<0.0001). The mean duration of hospital stay was 9 days higher in the PTD group (p<0.001). PTD group also had higher odds of transferring to ICU (OR = 9.4, p = 0.002), need for mechanical ventilation (OR = 10.1, p = 0.002) and death (OR = 10.3, p = 0.001). 32.6% had complete PTD recovery during follow-up. CONCLUSION: Proximal tubular dysfunction is highly prevalent in COVID-19 patients very early in the disease and may act as a predictor of AKI, ICU transfer, need for mechanical ventilation and death.

Identification of novel and potential inhibitors against the dengue virus NS2B/NS3 protease using virtual screening and biomolecular simulations.

Approximately 3.9 billion individuals are vulnerable to dengue infection, a prevalent cause of tropical diseases worldwide. Currently, no drugs are available for preventing or treating Flavivirus diseases, including Dengue, West Nile, and the more recent Zika virus. The highly conserved Flavivirus NS2B-NS3 protease, crucial for viral replication, is a promising therapeutic target. This study employed in-silico methodologies to identify novel and potentially effective anti-dengue small molecules. A pharmacophore model was constructed using an experimentally validated NS2B-NS3 inhibitor, with the Gunner Henry score confirming the model's validity. The Natural Product Activity and Species Source (NPASS) database was screened using the validated pharmacophore model, yielding a total of 60 hits against the NS2B-NS3 protease. Furthermore, the docking finding reveals that our newly identified compounds from the NPASS database have enhanced binding affinities and established significant interactions with allosteric residues of the target protein. MD simulation and post-MD analysis further validated this finding. The free binding energy was computed in terms of MM-GBSA analysis, with the total binding energy for compound 1 (-57.3 ± 2.8 and - 52.9 ± 1.9 replica 1 and 2) indicating a stronger binding affinity for the target protein. Overall, this computational study identified these compounds as potential hit molecules, and these findings can open up a new avenue to explore and develop inhibitors against Dengue virus infection.

Assessment of post-SARS-CoV-2 fatigue among physicians working in COVID-designated hospitals in Dhaka, Bangladesh.

BACKGROUND: Fatigue has been observed after the outbreaks of several infectious diseases around the world. To explore the fatigue level among physicians working in COVID-19-designated hospitals in Bangladesh, a matched case‒control study was conducted on post-SARS-CoV-2 fatigue. METHOD: In this study, 105 physicians diagnosed with COVID-19 who were declared cured at least 6 weeks before the interview date were recruited as cases, and the same number of age- and designation-matched healthy physicians were recruited as controls from the same hospital at a 1:1 ratio. Diagnosis of COVID-19 infection was confirmed by detection of SARS CoV-2 antigen by RT‒PCR from reference laboratories in Bangladesh or by HRCT chest. RESULT: Approximately two-thirds of the physicians were male (67.6% vs. 32.4%). More than 80% of them were younger than 40 years. The cases had a significantly greater number of comorbid conditions. The fatigue severity scale (FSS) score (mean) was much higher for cases (36.7 ± 5.3 vs. 19.3 ± 3.8) than for the control group, with a statistically significant difference. Similarly, approximately 67.7% of the previously COVID-19-positive physicians were in the highest FSS score tertile compared to the respondents in the control group, who had a mean score of <3. CONCLUSION: Physicians who had a previous history of COVID-19 infection had significantly higher total and mean FSS scores, signifying a more severe level of fatigue than physicians who had never been COVID-19 positive while working in the same hospital irrespective of their age and sex.

Navigating the microbial maze: unraveling the connection between gut microbiome and pediatric kidney and urinary tract disease.

The gut microbiome is made up of trillions of bacteria, viruses, archaea, and microbes that play a significant role in the maintenance of normal physiology in humans. Recent research has highlighted the effects of the microbiome and its dysbiosis in the pathogenesis and maintenance of kidney disease, especially chronic kidney disease (CKD) and its associated cardiovascular disease. While studies have addressed the kidney-microbiome axis in adults, how dysbiosis may uniquely impact pediatric kidney disease patients is not well-established. This narrative review highlights all relevant studies focusing on the microbiome and pediatric kidney disease that were published between 7/2015 and 7/2023. This review highlights pediatric-specific considerations including growth and bone health as well as emphasizing the need for increased pediatric research. Understanding microbiome-kidney interactions may allow for novel, less invasive interventions such as dietary changes and the use of probiotics to improve preventive care and ameliorate long-term morbidity and mortality in this vulnerable population.

DDI Prediction with Heterogeneous Information Network - Meta-Path Based Approach.

Drug-drug interaction (DDI) indicates where a particular drug's desired course of action is modified when taken with other drug (s). DDIs may hamper, enhance, or reduce the expected effect of either drug or, in the worst possible scenario, cause an adverse side effect. While it is crucial to identify drug-drug interactions, it is quite impossible to detect all possible DDIs for a new drug during the clinical trial. Therefore, many computational methods are proposed for this task. This paper presents a novel method based on a heterogeneous information network (HIN), which consists of drugs and other biomedical entities like proteins, pathways, and side effects. Afterward, we extract the rich semantic relationships among these entities using different meta-path-based topological features and facilitate DDI prediction. In addition, we present a heterogeneous graph attention network-based end-to-end model for DDI prediction in the heterogeneous graph. Experimental results show that our proposed method accurately predicts DDIs and outperforms the baselines significantly.

Therapeutic Promises of Ferulic Acid and its Derivatives on Hepatic damage Related with Oxidative Stress and Inflammation: A Review with Mechanisms.

Ferulic acid (FA) is a naturally occurring phenolic compound commonly found in the plant Ferula communis. This study aims to investigate the hepatoprotective effect of FA and its derivatives (methyl ferulic acid and trans-ferulic acid) against oxidative stress and inflammation-related hepatotoxicity due to toxicants based on the results of different non-clinical and preclinical tests. For this, data was collected from different reliable electronic databases such as PubMed, Google Scholar, and ScienceDirect, etc. The results of this investigation demonstrated that FA and its derivatives have potent hepatoprotective effects against oxidative stress and inflammation-related damage. The findings also revealed that these protective effects are due to the antioxidant and anti-inflammatory effects of the chemical compound. FA and its analogues significantly inhibit free radical generation and hinder the effects of proinflammatory markers and inflammatory enzymes, resulting in diminished cytotoxic and apoptotic hepatocyte death. The compounds also prevent intracellular lipid accumulation and provide protective effects.

Stakeholder engagement to introduce a standardised register for improved inpatient care of newborns and sick children in Bangladesh.

Background: Despite a global decrease of 59% in under-five mortality rates from 1990 to 2021, child survival remains a pressing issue. This holds true for Bangladesh, as well. In response, the Government of Bangladesh introduced a standardised register for strengthening the inpatient management of newborns and sick children in 2021. Methods: We employed a comprehensive four-phase stakeholder engagement process to implement an inpatient register for newborns and sick children. The first stage included identifying and prioritising potential stakeholders at the national and district levels. We identified eight organisations involved in newborn and child health and selected 24 participants from various other sectors for workshops aimed at raising awareness about the register's introduction. These stakeholders also participated in the register's design, development strategies planning, and implementation phases. These phases were led by the 'National Newborn Health and IMCI programme' with support from various partners. A technical working group reviewed existing registers and helped prepare training materials. Feedback from each workshop was crucial in finalising the register. Results: The Government of Bangladesh has recognised the need for an indoor register for newborns and sick children, which was to be established in collaboration with development partners. This initiative can enhance the quality of care for sick children and increase service provider accountability. Due to its successful implementation, it will continue to be used in the Kushtia and Dinajpur districts, with plans for a nationwide scale-up. The Government has allocated funds in the next health sector programme for orientation and register printing. A strengths, weaknesses, opportunities, and threats (SWOT) analysis of the stakeholder engagement process highlighted strengths such as a context-specific approach and collaborative engagement, as well as challenges such as time resource requirements. Conclusions: Implementing an inpatient register for newborns and sick children through stakeholder engagement can effectively improve child health care services. Aside from challenges such as resource intensiveness and stakeholder commitments, success depended on the organising authority's expertise in relationship building, budget allocation, time management, and workforce dedication. Therefore, strategic planning, staff recruitment, networking, and budgeting are crucial for successful stakeholder engagement and health care initiatives.

Introducing a standardised register for strengthening the inpatient management of newborns and sick children: Implementation research in selected health facilities of Bangladesh.

Background: It is imperative to maintain accurate documentation of clinical interventions aimed at enhancing the quality of care for newborns and sick children. The National Newborn Health and IMCI programme of Bangladesh led the development of a standardised register for managing newborns and sick children under five years of age during inpatient care through stakeholder engagement. We aimed to assess the implementation outcomes of the standardised register in the inpatient department. Methods: We conducted implementation research in two district hospitals and two sub-district hospitals of Kushtia and Dinajpur districts from November 2022 to January 2023 to assess the implementation outcomes of the standardised register. We assessed the following World Health Organization implementation outcome variables: usability, acceptability, adoption (actual use), fidelity (completeness and accuracy), and utility (quality of care) of the register against preset benchmarks. We collected data through structured interviews with health care providers; participant enrolment; and data extraction from inpatient registers and case record forms. Results: The average usability and acceptability scores among health care providers were 73 (standard deviation (SD) = 14) and 82 (SD = 14) out of 100, respectively. The inpatient register recorded 96% (95% confidence interval (CI) = 95-97) of under-five children who were admitted to the inpatient department (adoption - actual use). The proportions of completed data elements in the inpatient register were above the preset benchmark of 70% for all the assessed data elements except 'investigation done' (24%; 95% CI = 23-26) (fidelity - completeness). The percentage agreements between government-appointed nurses posted and study-appointed nurses were above the preset benchmark of 70% for all the reported variables (fidelity - accuracy). The kappa coefficient for the overall level of agreement between these two groups regarding reported variables indicated moderate to substantial agreement. The proportion of newborns with sepsis receiving injectable antibiotics was 62% (95% CI = 47-75) (utility - quality of care). We observed some variability in the completeness and accuracy of the inpatient register by district and facility type. Conclusions: The inpatient register was positively received by health care providers, with evaluations of implementation outcome variables showing encouraging results. Our findings could inform evidence-based decision-making on the implementation and scale-up of the inpatient register in Bangladesh, as well as other low- and middle-income countries.

Exploring Zingiber officinale bioactive compounds for inhibitory effects on Streptococcus pneumoniae capsular polysaccharide biosynthesis proteins: In silico study.

The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.

A context-driven approach through stakeholder engagement to introduce a digital emergency obstetric and newborn care register into routine obstetric health care services in Bangladesh.

Background: Emergency obstetric and newborn care (EmONC) in Bangladesh focusses on maternal health, whereby it addresses childbirth and postpartum complications to ensure women's health and well-being. It was transitioned to a digital platform to overcome challenges with the paper-based EmONC register and we conducted implementation research to assess the outcome. Here we outline the stakeholder engagement process integral to the implementation research process. Methods: We adopted a four-step stakeholder engagement model based on the identification, sensitisation, involvement, and engagement of stakeholders. The approach was informed by previous experience, desk reviews, and expert consultations to ensure comprehensive engagement with stakeholders at multiple levels. Led by the Maternal Health Programme of the Government of Bangladesh, we involved high-power and high-interest stakeholders in developing a joint action plan for digitisation of the paper-based EmONC register. Finally, we demonstrated this digital EmONC register in real-life settings to stakeholders at different levels. Results: The successful demonstration process fostered government ownership and collaboration with multiple stakeholders, while laying the foundation for scalability and sustainability. Nevertheless, our experience highlighted that the stakeholder engagement process is context-driven, time-consuming, resource-intensive, iterative, and dynamic, and it requires involving stakeholders with varied expertise. Effective strategic planning, facilitation, and the allocation of sufficient time and resources are essential components for successful stakeholder engagement. Conclusions: Our experience demonstrates the potential of adopting the 'identification, sensitisation, involvement, and engagement' stakeholder engagement model. Success in implementing this model in diverse settings depends on leveraging knowledge gained during implementation, maintaining robust communication with stakeholders, and harnessing the patience and determination of the facilitating organisation.

Recent Insights into the Antimicrobial Properties of Phyllanthus emblica L.: A Comprehensive Review of Wonder Berry.

Phyllanthus emblica L., or Amla, is known for its therapeutic properties and has been used as a medicinal plant. It is rich in vitamin C and other bioactive phytochemicals like polyphenols, gallic acid, chebulagic acid, leutolin, quercetin, etc. Different parts of this plant are used to treat various viral, bacterial, and fungal diseases. This review article summarizes the recent literature relevant to the antiviral, antibacterial, and antifungal effects of P. emblica. A variety of bacteria (Staphylococcus aureus, Bacillus subtillus, Enterococcus faecalis, Salmonella typhi, and Escherichia, etc.), fungi (Alternaria alternate Botroyodiplodia theobromae, Colletotrichum corcori, Curvularia lunata, Fusarium exquisite, Fusarium solanii, Aspergillus niger, Candida albicans, Colletotrichum gleosparoitis, and Macrophomina phaseolina) and viruses, like  Influenza A virus strain H3N2, hepatitis B, Human Immunodeficiency virus type-1 (HIV-1), Simplex virus type 1 (HSV-1) and type 2 (HSV-2) have experimented. Different techniques were used based on the way of identification. `For example, disc diffusion, dilution methods, sound diffusion, Immuno-peroxidase monolayer assay, serum HBV and HBsAg assay, enzyme immunoassay, etc. The present review analyzed and summarized the antimicrobial activities of P. emblica and possible mechanisms of action to provide future directions in translating these findings clinically.

Introducing a digital emergency obstetric and newborn care register for indoor obstetric patient management: An implementation research in selected public health care facilities of Bangladesh.

Background: Digital health records have emerged as vital tools for improving health care delivery and patient data management. Acknowledging the gaps in data recording by a paper-based register, the emergency obstetric and newborn care (EmONC) register used in the labour ward was digitised. In this study, we aimed to assess the implementation outcome of the digital register in selected public health care facilities in Bangladesh. Methods: Extensive collaboration with stakeholders facilitated the development of an android-based electronic register from the paper-based register in the labour rooms of the selected district and sub-district level public health facilities of Bangladesh. We conducted a study to assess the implementation outcome of introducing the digital EmONC register in the labour ward. Results: The digital register demonstrated high usability with a score of 83.7 according to the system usability scale, and health care providers found it highly acceptable, with an average score exceeding 95% using the technology acceptance model. The adoption rate reached an impressive 98% (95% confidence interval (CI) = 98-99), and fidelity stood at 90% (95% CI = 88-91) in the digital register, encompassing more than 80% of data elements. Notably, fidelity increased significantly over the implementation period of six months. The digital system proved a high utility rate of 89% (95% CI = 88-91), and all outcome variables exceeded the predefined benchmark. Conclusions: The implementation outcome assessment underscores the potential of the digital register to enhance maternal and newborn health care in Bangladesh. Its user-friendliness, improved data completeness, and high adoption rates indicate its capacity to streamline health care data management and improve the quality of care.

A mechanistic insight into the anticancer potentials of resveratrol: Current perspectives.

Resveratrol is a widely recognized polyphenolic phytochemical found in various plants and their fruits, such as peanuts, grapes, and berry fruits. It is renowned for its several health advantages. The phytochemical is well known for its anticancer properties, and a substantial amount of clinical evidence has also established its promise as a chemotherapeutic agent. This study focuses on assessing the anticancer properties of resveratrol and gaining insight into the underlying molecular mechanisms. It also evaluates the biopharmaceutical, toxicological characteristics, and clinical utilization of resveratrol to determine its suitability for further development as a reliable anticancer agent. Therefore, the information about preclinical and clinical studies was collected from different electronic databases up-to-date (2018-2023). Findings from this study revealed that resveratrol has potent therapeutic benefits against various cancers involving different molecular mechanisms, such as induction of oxidative stress, cytotoxicity, inhibition of cell migration and invasion, autophagy, arresting of the S phase of the cell cycle, apoptotic, anti-angiogenic, and antiproliferative effects by regulating different molecular pathways including PI3K/AKT, p38/MAPK/ERK, NGFR-AMPK-mTOR, and so on. However, the compound has poor oral bioavailability due to reduced absorption; this limitation is overcome by applying nanotechnology (nanoformulation of resveratrol). Clinical application also showed therapeutic benefits in several types of cancer with no serious adverse effects. We suggest additional extensive studies to further check the efficacy, safety, and long-term hazards. This could involve a larger number of clinical samples to establish the compound as a reliable drug in the treatment of cancer.

Financial regulations and sustainability: The role of energy price and climate policy uncertainty.

Russia ranks among the top five countries worldwide in terms of carbon emissions, with the energy, transportation, and manufacturing sectors as the major contributors. This poses a significant threat to both current and future generations. Russia faces challenges in achieving Sustainable Development Goal 13, necessitating the implementation of more innovative policies to promote environmental sustainability. Considering this alarming situation, this study investigates the role of financial regulations, energy price uncertainty, and climate policy uncertainty in reshaping sectoral CO2 emissions in Russia. This study utilizes a time-varying bootstrap rolling-window causality (BRW) approach using quarterly data from 1990 to 2021. The stability test for parameters indicates instability, suggesting that the full sample causality test may yield incorrect inferences. Thus, the BRW approach is employed for valid inferences. Our findings confirm the time-varying negative impact of financial regulations on CO2 emissions from energy, manufacturing, and transportation sectors. Additionally, findings confirm time-varying positive impact of energy prices and climate policy uncertainty on CO2 emissions from the energy, manufacturing, and transportation sectors. Strong financial regulations and stable energy and climate policies are crucial for achieving sustainability, highlighting significant policy implications for policymakers and stakeholders.

Therapeutic Promises of Bioactive Rosavin: A Comprehensive Review with Mechanistic Insight.

Rosavin is an alkylbenzene diglycoside primarily found in Rhodiola rosea (L.), demonstrating various pharmacological properties in a number of preclinical test systems. This study focuses on evaluating the pharmacological effects of rosavin and the underlying molecular mechanisms based on different preclinical and non-clinical investigations. The findings revealed that rosavin has anti-microbial, antioxidant, and different protective effects, including neuroprotective effects against various neurodegenerative ailments such as mild cognitive disorders, neuropathic pain, depression, and stress, as well as gastroprotective, osteoprotective, pulmoprotective, and hepatoprotective activities. This protective effect of rosavin is due to its capability to diminish inflammation and oxidative stress. The compound also manifested anticancer properties against various cancer via exerting cytotoxicity, apoptotic cell death, arresting the different phases (G0/G1) of the cancerous cell cycle, inhibiting migration, and invading other organs. Rosavin also regulated MAPK/ERK signaling pathways to exert suppressing effect of cancer cell. However, because of its high-water solubility, which lowers its permeability, the phytochemical has low oral bioavailability. The compound's relevant drug likeness was evaluated by the in silico ADME, revealing appropriate drug likeness. We suggest more extensive investigation and clinical studies to determine safety, efficacy, and human dose to establish the compound as a reliable therapeutic agent.

Anti-inflammatory activity of d-pinitol possibly through inhibiting COX-2 enzyme: in vivo and in silico studies.

Introduction: D-pinitol, a naturally occurring inositol, has diverse biological activities like antioxidant, antimicrobial and anticancer activities. This study aimed to evaluate anti-inflammatory effect of d-pinitol in a chick model. Additionally, in silico studies were performed to evaluate the molecular interactions with cyclooxygenase-2 (COX-2). Methods: The tested groups received d-pinitol (12.5, 25, and 50 mg/kg) and the standard drugs celecoxib and ketoprofen (42 mg/kg) via oral gavage prior to formalin injection. Then, the number of licks was counted for the first 10 min, and the paw edema diameter was measured at 60, 90, and 120 min. Results and Discussion: The d-pinitol groups significantly (p < 0.05) reduced the number of paw licks and paw edema diameters, compared to negative control. When d-pinitol was combined with celecoxib, it reduced inflammatory parameters more effectively than the individual groups. The in silico study showed a promising binding capacity of d-pinitol with COX-2. Taken together, d-pinitol exerted anti-inflammatory effects in a dose-dependent manner, possibly through COX-2 interaction pathway.

Gigantol, a promising natural drug for inflammation: a literature review and computational based study.

Gigantol, a bibenzyl compound extracted from various medicinal plants, has shown a number of biological activities, making it an attractive candidate for potential medical applications. This systematic review aims to shed light on gigantol's promising role in inflammation treatment and its underlying mechanisms. Gigantol exhibits potential anti-inflammatory properties in pre-clinical pharmacological test systems. It effectively reduced the levels of pro-inflammatory markers and arachidonic acid metabolites through various pathways, such as NF-κB, AKT, PI3K, and JNK/cPLA2/12-LOX. The in-silico investigations demonstrated that the MMP-13 enzyme served as the most promising target for gigantol with highest binding affinity (docking score = -8.8 kcal/mol). Encouragingly, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of gigantol confirmed its compatibility with the necessary physiochemical, pharmacokinetic, and toxicity properties, bolstering its potential as a drug candidate. Gigantol, with its well-documented anti-inflammatory properties, could be a promising agent for treating inflammation in the near future.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.