Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model.

AIM: The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. METHOD: Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. RESULT: The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, -27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. CONCLUSION: Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review.

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as 'Bhumyamalaki' (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.

Some distance measures for pythagorean cubic fuzzy sets: Application selection in optimal treatment for depression and anxiety.

Pythagorean cubic fuzzy sets represent an advancement beyond conventional interval-valued Pythagorean sets, integrating the principles of Pythagorean fuzzy sets and interval-valued Pythagorean fuzzy sets. Given the critical significance of distance measures in real-world decision-making and pattern recognition tasks, it is noteworthy that there exists a notable gap in the literature regarding distance measures specifically tailored for Pythagorean cubic fuzzy sets. The objectives of this paper are:•To define novel generalized distance measures between Pythagorean cubic fuzzy sets (PCFSs) to tackle intricate decision-making challenges.•These novel distance measures are undergoing testing on a real-world scenario concerning the management of anxiety and depression to evaluate their effectiveness and practical application.•We have illustrated the boundedness and nonlinear characteristics inherent in these distance measures. In addition, we conduct comparative analyses with existing approaches to validate the proposed methodology, thereby providing insights into its advantages and potential applications.

Centre-level variation in the survival of patients receiving haemodialysis in India: findings from a nationwide private haemodialysis network.

Background: There are no large studies examining survival in patients receiving haemodialysis in India or considering centre-level effects on survival. We measured survival variation between dialysis centres across India and evaluated the extent to which differences are explained by measured centre characteristics. Methods: This is a multilevel analysis of patient survival in centres of the NephroPlus dialysis network consisting of 193 centres across India. Patients receiving haemodialysis at a centre for ≥90 days between April 2014 and June 2019 were included, with analyses restricted to centres with ≥10 such patients. The primary outcome was all-cause mortality, measured from 90 days after joining a centre. Proportional hazards models with shared frailty were used to model centre- and patient-level effects on survival. Findings: Amongst 23,601 patients (median age 53 years; 29% female), the unadjusted centre-specific 180-day Kaplan-Meier survival estimates ranged between 55% (95% confidence interval [CI] 38-80%) and 100%, with a median of 88% (interquartile interval 83%-92%). After accounting for multilevel factors, estimated 180-day survival ranged between 83% (73-89%) and 97% (95-98%), with 90% 180-day survival in the average centre. The mortality rate in patients attending rural centres was 32% (Hazard Ratio 1.32; 95% CI 1.06-1.65) higher than those at urban centres in adjusted analyses. Multiple patient characteristics were associated with mortality. Interpretation: This is the first national benchmark for survival amongst dialysis patients in India. Centre- and patient-level characteristics are associated with survival but there remains unexplained variation between centres. As India continues to widen dialysis access, ongoing quality improvement programs will be an important part of ensuring that patients experience the best possible outcomes at the point of care. Funding: This project received no external funding.

Schiff Bases: A Captivating Scaffold with Potential Anticonvulsant Activity.

One of the most important organic compounds, also known as a Schiff base, imine, or azomethine, has been associated with several biological processes. The group is a component of both natural or synthetic chemicals and functions as both a precursor and an intermediary in the synthesis of therapeutically active substances. The review highlights the various non-metal Schiff bases' structure-activity relationship (SAR) studies, general model, docking, and design approach for anticonvulsant actions. Schiff bases serve as linkers in numerous synthetic compounds with a variety of activities, according to the findings of several investigations. As a result, the current review will give readers a thorough understanding of the key ideas put forth by different researchers regarding the anticonvulsant properties of Schiff bases. It will serve as a valuable information source for those planning to synthesize new anticonvulsant molecules that contain Schiff bases as pharmacophores or biologically active moieties.

Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning.

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.

Fuzzy analysis of 2-D wave equation through Hukuhara differentiability coupled with AOS technique.

The research article in hand provides a new mechanism that deals with the investigation of the triangular analytical fuzzy solutions (TAFS) of the two-dimensional fuzzy fractional order wave equation (2-D FFWE) through the Hukuhara conformable fractional derivative (HCFD) along with the concept of [gH] and [gH-p] differentiability. The mechanism consists of a fuzzy traveling wave method coupled with additive operating splitting (AOS). The procedure for the aforesaid mechanism starts with the extension of the HCFD to the fuzzy conformable fractional derivative (FCFD). Furthermore, some properties of FCFD that play a vital role in this study like, ([i-gH],[ii-gH],[i-p],[ii-p])-differentiability, switching point, fuzzy chain rule, and traveling wave method are discussed in detail. Further, fuzzy traveling wave method coupled with the procedure of the additive operating splitting (AOS) method is adopted to investigate the triangular analytical fuzzy solution of the Two-dimensional fuzzy wave equation (2-D FWE). Finally, some examples are provided that support our arguments.

Are we Using the Right Evidence to Inform Suicide Prevention in Low- and Middle-Income Countries? An Umbrella Review.

OBJECTIVE: Suicide disproportionately affects low- and middle-income countries and evidence regarding prevention approaches developed in high income countries may not be applicable in these settings. We conducted an umbrella review to assess whether the conclusions of suicide prevention systematic reviews accurately reflect the studies contained within those reviews in terms of setting generalizability. METHODS: We conducted database searches in PubMed/Medline, Embase, PsycInfo, PsychExtra, OVID global health, and LILACS/BECS. We included systematic reviews with the outcome of suicide, including bereavement studies where suicide death was also the exposure. RESULTS: Out of the 147 reviews assessed, we found that over 80% of systematic reviews on suicide deaths do not provide an accurate summary of review findings with relation to geographic relevance and ultimately generalizability. CONCLUSION: Systematic reviews are often the resource used by practitioners and policymakers to guide services. Misleading reviews can detrimentally impact suicide prevention efforts in LMICs. We call for systematic reviewers to be responsible when generalizing the findings of their reviews particularly in the abstracts.

Delivery of nano-emulgel carrier: optimization, evaluation and in vivo anti-inflammation estimations for osteoarthritis.

Aim: Optimization and evaluation of Aceclofenac nanoemulgel for treatment for rheumatoid arthritis and reduction of GI irritation and enhancement of bioavaibility. Materials & methods: Different batches of emulgel and selected batch was proceeded for characterization like particle size, scanning electron microscopy, drug ingredient, in vitro release, Fourier transform infrared and x-ray diffraction in vitro inflammation and gel evaluation such as (spreadability, swelling index), ex vitro permeation, skin irritation and in vivo anti-inflammatory. Result: Emulgel showed nanometri size sustained release (79.96% in 6 h), compatibility and anti-inflammatory activity compared with pure drug. Concluded that emulgels had better (nearly twice as good) anti-inflammatory action as the commercial product. Conclusion: Compared with the commercial gel, the emulgel's anti-inflammatory effect had a quicker onset and a longer duration of action.

A non-steroidal anti-inflammatory drug (NSAID) aceclofenac is used as the treatment for rheumatoid arthritis. It is generally taken orally. However, there are a few issues with it being taken this way. The main ones are: some of the drug reacts too early in the body, meaning only a small amount of it reaches the parts of the body where it is needed; it can irritate the digestive system; and it does not dissolve very well in water, which also makes it harder to reach the parts of the body where it is needed. The authors of this study created a new type of gel for people to rub into their skin, instead of taking a pill. They hoped that this would allow the drug to be absorbed more directly into the parts of the body where it was needed, without irritating the digestive system. They tested the gel to see how well it contained and released the drug, how well it absorbed into the skin, and whether it irritated the skin. They found that the gel contained and released the drug more effectively than similar gels which are already available and caused less irritation to the skin.

Statistical and computational analysis for corruption and poverty model using Caputo-type fractional differential equations.

Since there is a clear correlation between poverty and corruption, mathematicians have been actively researching the concept of poverty and corruption in order to develop the optimal strategy of corruption control. This work aims to develop a mathematical model for the dynamics of poverty and corruption. First, we study and analyze the indicators of corruption and poverty rates by applying the linear model along with the Eviews program during the study period. Then, we present a prediction of poverty rates for 2023 and 2024 using the results of the standard problem-free model. Next, we formulate the model in the frame of Caputo fractional derivatives. Fundamental properties, including equilibrium points, basic reproduction number, and positive solutions of the considered model are obtained using nonlinear analysis. Sufficient conditions for the existence and uniqueness of solutions are studied via using fixed point theory. Numerical analysis is performed by using modified Euler method. Moreover, results about Ulam-Hyers stability are also presented. The aforementioned results are presented graphically. In addition, a comparison with real data and simulated results is also given. Finally, we conclude the work by providing a brief conclusion.

A Review on Molecular Docking As an Interpretative Tool for Molecular Targets in Disease Management.

One of the most often utilized methods for drug discovery is molecular docking. With docking, one may discover new therapeutically relevant molecules by targeting the molecule and predicting the target-ligand interactions as well as different conformation of ligand at various positions. The prediction signifies the effectiveness of the molecule or the developed molecule having different affinity with target. Drug discovery plays an important role in the development of a new drug molecule of different moiety attached to it, which leads us in the management of several diseases. In silico approach led us to identification of numerous diseases caused by virus, fungi, bacteria, protozoa, and other microorganisms that affect human health. By means of computational approach, we can categorize disease symptoms and use the drugs available for such types of warning signs. After the docking process, molecular dynamics computational technique helps in the simulation of the physical movement of atoms and molecules for a fixed period of time, giving a view of the dynamic evaluation of the system. This review is an attempt to illustrate the role of molecular docking in drug development.

Mini Review on Clinical Aspects of Monkeypox.

Monkeypox is a disease caused by the monkeypox virus, which is a type of orthopox virus that comes from the virus family Poxviridae. Its first case reported in animals and humans was in 1958 and 1970, respectively. It is a viral zoonosis disease with two modes of transmission: animal to human (via direct contact or eating the meat of an infected animal) and human to human (via contact or contact with skin lesions, body fluids, and infected person's contaminated objects). The literature depicts that monkeypox is less contagious among individuals in contrast to smallpox; the infection chain of monkeypox is nearly five to six patients approximately. It has two clades, the West African and the Central African (the Congo basin). The Congo basin subgroup of monkeypox is highly transmissible and severe. The symptoms of monkeypox include fever, lethargy, headache, lymphadenopathy, myalgia, myodynia, fainting, shivers, backache, and rashes on the face and extremities. The most common symptom of monkeypox is lymphatic hyperplasia or, lymph adenopathy or swollen lymph nodes. It is proven to be very useful in the diagnosis of monkeypox. The antiviral drugs that are used for its treatment are tecovirimat, brincidofovir and cidofovir. Tecovirimat has fewer side effects and it shows better therapeutic action in comparison to brincidofovir and cidofovir. For the prevention of monkeypox, the Center for Disease Control and Prevention recommends the administration of the same vaccine used for smallpox named INVAMUNE, which is currently in its third generation. Its first and second generations have adverse side effects in patients having HIV or atopic dermatitis.

Review on the Artificial Intelligence-based Nanorobotics Targeted Drug Delivery System for Brain-specific Targeting.

Contemporary medical research increasingly focuses on the blood-brain barrier (BBB) to maintain homeostasis in healthy individuals and provide solutions for neurological disorders, including brain cancer. Specialized in vitro modules replicate the BBB's complex structure and signalling using micro-engineered perfusion devices and advanced 3D cell cultures, thus advancing the understanding of neuropharmacology. This research explores nanoparticle-based biomolecular engineering for precise control, targeting, and transport of theranostic payloads across the BBB using nanorobots. The review summarizes case studies on delivering therapeutics for brain tumors and neurological disorders, such as Alzheimer's, Parkinson's, and multiple sclerosis. It also examines the advantages and disadvantages of nano-robotics. In conclusion, integrating machine learning and AI with robotics aims to develop safe nanorobots capable of interacting with the BBB without adverse effects. This comprehensive review is valuable for extensive analysis and is of great significance to healthcare professionals, engineers specializing in robotics, chemists, and bioengineers involved in pharmaceutical development and neurological research, emphasizing transdisciplinary approaches.

Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson's Disease.

Neurological ailments, including stroke, Alzheimer's disease (AD), epilepsy, Parkinson's disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain's substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019-2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD.

E-Cigarettes and Associated Health Risks: An Update on Cancer Potential.

The potential cancer risk associated with electronic-cigarette (e-cigarette) use is ongoing and remains a subject of debate. E-Cigarettes work by heating a liquid that usually contains nicotine, flavorings, and other chemicals. When the liquid is heated, users inhale an aerosol into their lungs. While e-cigarettes are generally considered less harmful than traditional tobacco products, they still contain potentially harmful chemicals, which can damage DNA and lead to cancer. Several studies have investigated the potential cancer risk associated with e-cigarette use, while other studies have suggested that e-cigarette aerosol may contain carcinogenic chemicals that could increase the risk of lung and bladder cancer in humans. However, these studies are limited in their scope and do not provide conclusive evidence. Overall, the long-term cancer risk associated with e-cigarette use remains uncertain, more research is needed to fully understand the potential risks and benefits of e-cigarettes. However, this review will allow the investigator to get more recent updates about e-cigarettes.

Reprocessing and reuse of dialyzers: A technological solution for balancing cost and quality in lower and middle-income countries.

Hemodialysis is the commonest kidney replacement therapy (KRT) globally and rapidly growing in developing countries, while in developed countries it is reaching a plateau. The penetration of hemodialysis (HD) varies widely among countries and is largely influenced by socioeconomics, healthcare financing, particularly by government, local infrastructure, healthcare workforce, health system characteristics, and affordability of the population. Biomedical equipment, consumables, disposables, and labor are major cost drivers of KRT. Implementing strategies to balance cost and quality of care is an arduous task for health care planning, delivery, and patient care in low- and middle-income countries. In this context, the cost of dialyzers which form a significant component of the recurring cost of HD can be reduced by reuse after appropriate reprocessing. But this practice is largely abandoned in developed countries because of concerns of safety. However, the evidence against the reuse of modern dialyzers is not robust and certainly not based on well-designed randomized trials. The industrialization of dialysis delivery, the interests of equipment manufacturers and the nature of dialysis delivery have propelled single use of dialyzers. In this context, developing countries needing to expand HD services access at low cost are caught at crossroads. Process improvements are needed to standardize reprocessing that prioritizes safety while maintaining effectiveness. Recent advances in mobile and internet technologies could make this an achievable reality. We propose such an approach that would ensure treatment effectiveness, patient and healthcare provider safety, efficient resource utilization, and cost control.

Utilization of Haar wavelet collocation technique for fractal-fractional order problem.

This work is devoted for establishing adequate results for the qualitative theory as well as approximate solution of "fractal-fractional order differential equations" (F-FDEs). For the required numerical results, we use Haar wavelet collocation (H-W-C) method which has very rarely utilized for F-FDEs. We establish the general algorithm for F-FDEs to compute numerical solution for the considered class. Also, we establish a result devoted to the qualitative theory via Banach fixed point result. A results devoted to Ulam-Hyers (U-H) stability are also included. Two pertinent examples are given along with the comparison and different norms of errors displayed in figures as well as tables.

Disposable platform for bacterial lysis and nucleic acid amplification based on a single USB-powered printed circuit board.

Recent advances in electronics and microfluidics have enabled several research groups to develop fully integrated, sample-to-result isothermal nucleic acid amplification test (NAAT) platforms for the point of care. However, high component counts and costs have limited translation of these platforms beyond the clinic to low-resource settings-including homes. Many NAATs include complex, multi-component heater electronics based on flex circuits or multiple printed circuit boards (PCBs) to support essential NAAT steps such as lysis, sample deactivation, and nucleic acid amplification. In contrast, current commercial assays for home use, such as those for pregnancy or ovulation that include electronics, typically have just one onboard PCB. This work describes a generalizable strategy to integrate all heaters and the electronics needed to control them onto a single low-cost, USB-powered PCB. We built a multiplexable disposable NAAT ("MD NAAT") platform that applies these principles, integrating small-area heaters that heat small regions to near-boiling (for pathogen lysis and deactivation) and large-area heaters (for amplification) on the same PCB. We show that both classes of heaters have high intra-board and inter-device reproducibility despite only heating a NAAT cartridge from below. We validated the small-area heaters by lysing methicillin-resistant Staphylococcus aureus (MRSA) cells and the large-area heaters by performing two types of isothermal NAATs (isothermal strand displacement amplification (iSDA) and loop-mediated isothermal amplification (LAMP)). These results demonstrate the merit of integrating NAAT heaters and control electronics onto a single printed circuit board and are a step toward translating NAATs to the home.

Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing.

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.

Fluro-Protein C-Phycocyanin Docked Silver Nanocomposite Accelerates Cell Migration through NFĸB Signaling Pathway.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.