Dengue fever coinfection in COVID-19 era: A public health concern.

Background and Aim: Dengue and SARS-CoV-2 coinfection is commonly encountered and constantly reported in particularly the dengue-endemic regions thus posing a co-epidemic threat. Coinfection is also significantly associated with morbidity and mortality. Comorbidity risk during a coinfection is of a greater concern. Although the pathophysiologies of the two infections vary, their identical clinical symptoms during coinfection result in diagnostic and therapeutic complexities. Methods: A literature search for the current relevant reports was carried out. The searched databases were Scopus, PubMed, Google Scholar and the Web of Science, with health agencies like the WHO. Based on the selection criteria, the most recent and pertinent reports published in English language were included for the ease of understanding, deciphering and analysing the secondary data. Results: A delay in proper diagnosis of coinfection could result in serious complications with poor patient outcome. Whether it is a standalone dengue or COVID-19 infection or a coinfection, specific biomarkers may be utilized for its foolproof diagnosis. This article highlights the various diagnostic techniques and immune responses from the perspective of prompt and appropriate public health management for patients suffering from COVID-19 and dengue viral coinfections, both being independently or collectively capable of damaging a human body. Conclusion: As coinfection poses significantly large burden on an already-fragile healthcare facility, constant monitoring of a coinfected patient is needed for prompt and suitable therapeutics. Also, to maintain high vigilance and invoke appropriate preventive measures particularly in dengue endemic regions, the government, healthcare authority and the general public need to collaborate and cooperate.

Envisioning Clinical Management of Breast Cancer: a Comprehensive Review.

Coming to the edge of disease manufacturing in the twenty-first-century, breast cancer occupies a terrifying scenario in the globe, especially in adult women. Its curiosity endeavours remarkable advances made during the past decennaries for cancer treatment and diagnosis.

In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes.

In spite of the fact that many medicinal plants have been truly utilized for the management of diabetes all through the world, very few of them have been reported scientifically. Recently, a diverse variety of animal models have been established to better understand the pathophysiology of diabetes mellitus, and new medications to treat the condition have been introduced in the market. Flavonoids are naturally occurring substances that can be found in plants and various foods and may have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable novel therapy option for macrovasular complications in preclinical models; however, human clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques and animal models. Natural compounds, mostly derived from plants, have been studied in diabetes models generated by chemical agents in the majority of research. The aim of this work was to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic agents. This review contributes to the scientist's design of new methodologies for the development of novel therapeutic agents having potential antihyperglycemic activity.

The neglected continuously emerging Marburg virus disease in Africa: A global public health threat.

Background and Aim: Severe viral hemorrhagic fever (VHF) is caused by Marburg virus which is a member of the Filoviridae (filovirus) family. Many Marburg virus disease (MVD) outbreaks are reported in five decades. A major notable outbreak with substantial reported cases of infections and deaths was in 2022 in Uganda. The World Health Organisation (WHO) reported MVD outbreak in Ghana in July 2022 following the detection of two probable VHF patients there. Further, the virus was reported from two other African countries, the Equatorial Guinea (February 2023) and Tanzania (March 2023). There have been 35 deaths out of 40 reported cases in Equatorial Guinea, and six of the nine confirmed cases in Tanzania so far. Methods: Data particularly on the several MVD outbreaks as reported from the African countries were searched on various databases including the Pubmed, Scopus, and Web-of-science. Also, the primary data and reports from health agencies like the WHO and the Centers for Disease Control and Prevention CDC) were evaluated and the efficacy reviewed. Results: Chiroptera in general and bat species like Rousettus aegyptiacus and Hipposideros caffer in particular are natural reservoirs of the Marburg virus. MVD-infected nonhuman primate African fruit-bat and the MVD-infected humans pose significant risk in human infections. Cross-border viral transmission and its potential further international ramification concerns raise the risk of its rapid spread and a potential outbreak. Occurrence of MVD is becoming more frequent in Africa with higher case fatality rates. Effective prophylactic and therapeutic interventions to counter this deadly virus are suggested. Conclusion: In the face of the lack of effective therapeutics and preventives against MVD, supportive care is the only available option which contributes to the growing concern and disease severity. In view of the preventive approaches involving effective surveillance and monitoring system following the "One Health" model is extremely beneficial to ensure a healthy world for all, this article aims at emphasizing several MVD outbreaks, epidemiology, zoonosis of the virus, current treatment strategies, risk assessments, and the mitigation strategies against MVD.

COVID-19 vaccines and their underbelly: Are we going the right way?

Background: Historically, a critical aetiological agent of health concern stays till eternity after its discovery, so shall it be with the COVID-19 outbreak. It has transformed human life to a 'new normal' with huge tolls on the social, psychological, intellectual and financial spheres. Aim: This perspective aimed to collate numerous reported COVID-19 vaccine-associated adverse events and the predisposing factors. It focussed on the efficacy of mix-n-match (cocktail) vaccines to effectively counter COVID-19 infection to facilitate future research and possible interventions. Material and Methods: Databases like Scopus, Pubmed and the Web-of-science were searched for published literature on 'adverse events associated with COVID-19 vaccine'. The reports and updates from health agencies like the WHO and CDC were also considered for the purpose. The details with respect to the adverse events associated with COVID-19 vaccination and the predisposing factors were compiled to obtain insights and suggest possible future directions in vaccine research. Results: India stood strong to manage its health resources in time and turned into a dominant global vaccine supplier at a time when healthcare infrastructure of many countries was still significantly challenged. Developing indigenous vaccines and the vaccination drive in India were its major achievements during the second and the subsequent COVID-19 waves. The fully indigenous Covaxin vaccine, primarily as an emergency intervention, was successfully rapidly launched. Similar such vaccines for emergency use were developed elsewhere as well. However, all of these reached the marketplace with a 'emergency use only' tag, without formal clinical trials and other associated formalities to validate and verify them as these would require much longer incubation time before they are available for human use. Discussion: Many adverse events associated with either the first or the second/booster vaccination doses were reported. Evidently, these associated adverse events were considered as 'usually rare' or were often underreported. Without the additional financial or ethical burden on the vaccine companies, fortunately, the Phase IV (human) clinical trials of their manufactured vaccines are occurring by default as the human population receives these under the tag 'emergency use'. Thus, focused and collaborative strategies to unveil the molecular mechanisms in vaccine-related adverse events in a time-bound manner are suggested. Conclusion: Reliable data particularly on the safety of children is lacking as majority of the current over-the-counter COVID-19 vaccines were for emergency use. Many of these were still in their Phase III and Phase IV trials. The need for a mutant-proof, next-gen COVID-19 vaccine in the face of vaccine-associated adverse events is opined.

Recent developments in nanoparticles for the treatment of diabetes.

Changes in the homeostasis of blood sugar levels are a hallmark of diabetes mellitus, an incurable metabolic condition, for which the first-line treatment is the subcutaneous injection of insulin. However, this method of administration is linked to low patient compliance because of the possibility of local infection, discomfort and pain. To enable the administration of the peptide through more palatable paths without requiring an injection, like by oral routes, the use of nanoparticles as insulin carriers has been suggested. The use of nanoparticles usually improves the bioavailability and physicochemical stability of the loaded medicine. The utilisation of several forms of nanoparticles (like lipid and polymeric nanoparticles, micelles, dendrimers, liposomes, niosomes, nanoemulsions and drug nanosuspensions) is discussed in this article as a way to improve the administration of various oral hypoglycaemic medications when compared to conventional treatments.

Deep and Transfer Learning Approaches for Automated Early Detection of Monkeypox (Mpox) Alongside Other Similar Skin Lesions and Their Classification.

The world faces multiple public health emergencies simultaneously, such as COVID-19 and Monkeypox (mpox). mpox, from being a neglected disease, has emerged as a global threat that has spread to more than 100 nonendemic countries, even as COVID-19 has been spreading for more than 3 years now. The general mpox symptoms are similar to chickenpox and measles, thus leading to a possible misdiagnosis. This study aimed at facilitating a rapid and high-brevity mpox diagnosis. Reportedly, mpox circulates among particular groups, such as sexually promiscuous gay and bisexuals. Hence, selectively vaccinating, isolating, and treating them seems difficult due to the associated social stigma. Deep learning (DL) has great promise in image-based diagnosis and could help in error-free bulk diagnosis. The novelty proposed, the system adopted, and the methods and approaches are discussed in the article. The present work proposes the use of DL models for automated early mpox diagnosis. The performances of the proposed algorithms were evaluated using the data set available in public domain. The data set adopted for the study was meant for both training and testing, the details of which are elaborated. The performances of CNN, VGG19, ResNet 50, Inception v3, and Autoencoder algorithms were compared. It was concluded that CNN, VGG19, and Inception v3 could help in early detection of mpox skin lesions, and Inception v3 returned the best (96.56%) classification accuracy.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Objective Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Methods Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. Results The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. Conclusion A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1C, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models.

The purpose of the study is to evaluate the antidiabetic and hyperlipidemic potential of stem bark extract of Premna spinosa (Lamiaceae), by using streptozotocin (STZ)-nicotinamide (NA)-induced diabetic and triton-induced hyperlipidemic models in albino rats. The blood glucose, total cholesterol, and triglyceride levels were determined in STZ-NA-induced diabetic and triton-induced hyperlipidemic rats, as per the respective protocols. It was found that there is the dose dependent and significant reduction in foregoing parameters on the administration of extract from Premna spinosa stem bark at the doses of 200, 400, and 800 mg/kg body weight to diabetic and hyperlipidemic rats. From these observed results it may be inferred that the stem bark of Premna spinosa possesses remarkable antidiabetic and antihyperlipidemic properties.

Preparation and in-vitro, in-vivo characterisation of pioglitazone loaded chitosan/PEG blended PLGA biocompatible nanoparticles.

The purpose of this research was to formulate Polymeric (Chitosan/PEG blended PLGA) nanoparticles containing Pioglitazone as a model drug using the solvent evaporation method. The resultant nanoparticles were characterized by dynamic laser spectroscopy, transmission electron microscopy, atomic force microscopy, and X-ray diffraction. The nanoparticles had a spherical shape with a mean particle diameter of 323 ± 1.15 nm. Furthermore, data from differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) research revealed no drug-polymer interaction. The efficiency of drug encapsulation was determined to be 61.7 ± 2.91%. The formulated nanoparticles also showed improved drug bioavailability in an in vivo system. When compared to the native drug-treated group, blood glucose levels in Pioglitazone-loaded nanoparticle treated streptozotocin caused diabetic rats were reduced dramatically (up to 7 days) to normal levels (up to 6 h). In albino rats, the nanoparticles' in vivo toxicity investigation revealed no significant changes in behavioral, biochemical, or hematological exams. As a result, the developed system may be useful in achieving a controlled release of the drug, which may help decrease dose frequency and increase patient compliance with pioglitazone for the treatment of type 2 diabetes mellitus.

Lomustine Incorporated Lipid Nanostructures Demonstrated Preferential Anticancer Properties in C6 Glioma Cell Lines with Enhanced Pharmacokinetic Profile in Mice.

Effective treatment of glioma still stands as a challenge in medical science. The work aims for the fabrication and evaluation of lipid based nanostructures for improved delivery of lomustine to brain tumor cells. Experimental formulations (LNLs) were developed by modified lipid layer hydration technique and evaluated for different in vitro characteristics like particle size analysis, surface charge, surface morphology, internal structure, in vitro drug loading, drug release profile etc. Anticancer potential of selected LNLs was tested in vitro on C6 glioma cell line. Electron microscopic study depicted a size of less than 50 nm for the selected LNLs along 8.8% drug loading with a sustained drug release tendency over 48 h study period. Confocal microscopy revealed extensive internalization of the selected LNL in C6 cells. LNLs were found more cytotoxic than free drug and blank nanocarriers as depicted from MTT assay. The selected LNL showed improved pharmacokinetic profile both in blood and brain in the experimental mice models along with negligible hemolysis in mice blood cells. Further studies are warranted for the future translation of LNLs at clinics.

Targeting to Brain Tumor: Nanocarrier-Based Drug Delivery Platforms, Opportunities, and Challenges.

Cancer is a class of disorder characterized by anomalous growth of cells escalating in an uncontrolled way. Among all the cancers, treatment of cancerous brain tumors has been a tough challenge for the research scientists. Moreover, the absence of early-stage symptoms delays its diagnosis, consequently worsening its severity. Conventional treatments such as surgery, radiation, and chemotherapy are still linked with several limitations. The therapeutic effect of most of the anticancer drugs is highly restricted by their inability to pass the blood-brain barrier, low solubility, limited therapeutic window, and so on. Alarming incidences of brain cases associated with low survival rate across the globe coupled with the inefficiency of current treatment strategies have forced the formulation scientists to investigate nanotechnology-based advanced therapeutic approaches to tackle the disease. Various nanoplatforms such as polymeric nanoparticles (NPs), nanoliposomes, dendrimers, carbon nanotubes, and magnetic NPs have been reported in the past years to improve the drug administration into brain tumor cells and to minimize their off-target distribution for lesser side effects and better treatment outcomes. The review presents updated information on the nanocarrier-based drug delivery systems reported in the past few years for the treatment of brain tumor along with new advancements in this field. It also throws some light on the recent challenges faced in the practical field for the successful clinical translation of such nanodrug carriers along with a discussion on the future prospects.

AQbD Driven Development of an RP-HPLC Method for the Quantitation of Abiraterone Acetate for its Pharmaceutical Formulations in the Presence of Degradants.

OBJECTIVES: Abiraterone acetate is a well-known anticancer drug and a steroidal derivative of progesterone for treatment of patients with hormone-refractory prostate cancer. Chemometrics-assisted reverse phase high performance liquid chromatography (RP-HPLC) development of the drug abiraterone acetate has been employed in this study using an analytical quality by design (AQbD) approach. MATERIALS AND METHODS: Drug separation was performed using a Princeton Merck-Hibar Purospher STAR (C18, 250 mm × 4.6 mm) i.d., 5 µm particle size) with ultraviolet detection at 235 nm. A Box-Behnken statistical experimental design with response surface methodology was executed for method optimization and desired chromatographic separation from its formulation with a few numbers of experimental trials. The impact of three independent variables, namely, composition of the mobile phase, pH, and flow rate, on response retention time and peak area was studied by constructing an arithmetic model from these variables. RESULTS: Optimized experimental conditions for the proposed work include the mobile phase acetonitrile and phosphate buffer (10 mM KH2PO4) (20:80 %v/v). At the concentration range of 2-100 µg/mL, a linear calibration curve was found. Recovery was performed at three concentrations and was foun to be between 98% and 102%. The 3D response surface curves revealed that mobile phase composition and flow rate were the most substantial critical factors affecting desired responses. CONCLUSION: An attempt has been made to develop and validate an economical, precise, robust, stability-indicating AQbD-based RP-HPLC method that can be employed successfully for the routine analysis of abiraterone acetate in quality control labs.

Poly-lactide-co-glycolide nanoparticles containing voriconazole for pulmonary delivery: in vitro and in vivo study.

Poly-lactide-co-glycolide nanoparticles (207-605 nm) containing voriconazole (VNPs) were developed using a multiple-emulsification technique and were also made porous during preparation in presence of an effervescent mixture for improved pulmonary delivery. Pulmonary deposition of the particles was studied using a customized inhalation chamber. VNPs had a maximum of 30% (w/w) drug loading and a zeta potential (ZP) value around -20 mV. In the initial 2 hours, 20% of the drug was released from VNPs, followed by sustained release for 15 days. Porous particles had a lower mass median aerodynamic diameter (MMAD) than nonporous particles. Porous particles produced the highest initial drug deposition (~120 µg/g of tissue). The drug was detectable in lungs until 7 days and 5 days after administration, for porous and nonporous particles, respectively. VNPs with improved drug loading were successfully delivered to murine lungs. Porous nanoparticles with lower MMADs showed better pulmonary deposition and sustained presence in lungs. FROM THE CLINICAL EDITOR: In this paper, voriconazole-containing porous nanoparticles were studied for inhalational delivery to lung infections in a murine model, demonstrating prolonged half-life and improved pulmonary deposition.

Nanobiotechnology-based drug delivery in brain targeting.

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeutics. The current challenges are to design and develop the drug delivery careers, which must be able to deliver the drug across the BBB at a safe and effective manner. Nanoparticles are found to be effective careers in delivery of conventional drugs, recombinant proteins, vaccines as well as nucleotides. Nanoparticlulate drug delivery systems are found to be improving in the pharmacokinetic strategies of the drug molecules such as biodistribution, bioavailability and drug release characteristics in a controlled and effective manner with site specific drug delivery targeting to tissue or cell with reduction in toxic manifestation. Therefore, the use of nanotechnology in the field of pharmaceutical biotechnology helps in improving the drug delivery strategy including the kinetics and therapeutic index to solve the delivery problems of some biotech drugs including the recombinant proteins and oligonucleotides. This review is made to provide an insight to the role of nanobiotechnology in drug delivery and drug targeting to brain and its recent advances in the field of drug delivery systems.

Submicron-size biodegradable polymer-based didanosine particles for treating HIV at early stage: an in vitro study.

Human immunodeficiency viruses (HIV) hide themselves in macrophages at the early stage of infection. Delivering drug in a sustained manner from polymeric nanoparticles in those cells could control the disease effectively. The study was intended to develop poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing didanosine and to observe their uptake by macrophages in vitro. Various physicochemical evaluations related to nanoparticles, such as drug-excipient interaction, surface morphology, particle size, zeta potential, polydispersity index, drug loading, in vitro drug release and nanoparticle-uptake by macrophages in vitro were determined. Homogenising speeds and drug-polymer ratio varied drug loading and polydispersity index of nanoparticles, providing sustained drug release. Dimethyl sulphoxide/polyethylene glycol improved drug loading predominantly. Nanoparticle-uptake by macrophages was concentration dependent. Experimental nanoparticles successfully transported didanosine to macrophages in vitro, suggesting reduction of dose, thus minimising toxicity and side effects. Developed nanoparticle may control HIV infection effectively at an early stage.

Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers.

Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly L-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study.