Kaempferol Regresses Carcinogenesis through a Molecular Cross Talk Involved in Proliferation, Apoptosis and Inflammation on Human Cervical Cancer Cells, HeLa

Kaempferol, a flavonoid, contains a plethora of therapeutic properties and has demonstrated its efficacy against cancer. This study aims to unravel the molecular targets that are being modulated by kaempferol on HeLa cells. Various assays were performed, namely: MTT assay, flow cytometry to analyze DNA content and quantitate apoptosis. Quantitative PCR and protein profiling were performed to evaluate the modulated manifestation of different genes involved in apoptosis, cell growth and inflammation. Kaempferol exhibited reduction in cell viability of HeLa cells (IC50 = 50 µM 48 h), whereas it did not show any significant effect on viability of the AC-16 cell line. Kaempferol-impacted apoptosis was definitive, as it induced DNA fragmentation, caused disruption of membrane potential, accumulation of cells in the G2-M phase and augmented early apoptosis. Consistently, kaempferol induced apoptosis in HeLa cells by modulating the expression of various genes at both transcript and protein levels. It upregulated the expression of pro-apoptotic genes, including APAF1, BAX, BAD, Caspases 3, and 9, etc., at the transcript level and Bad, Bax, p27, p53, p21, Caspases 3 and 8 etc. at the protein level, while it downregulated the expression of pro-survival gene BCL-2, BIRC8, MCL-1, XIAP, and NAIP at the transcript level and Bcl-2, XIAP, Livin, clap-2 at the protein level. Kaempferol attenuated oxidative stress by upregulating GSH activity and anti-inflammatory response by suppressing NF-kB pathways. Moreover, kaempferol averted rampant cell division and induced apoptosis by modulating AKT/MTOR and MAP kinase pathways. Hence, kaempferol can be considered as a natural therapeutic agent with a differential profile

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems

Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer-aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century

Antiarthritic Potential of <i>Calotropis procera</i> Leaf Fractions in FCA-Induced Arthritic Rats: Involvement of Cellular Inflammatory Mediators and Other Biomarkers

Calotropis procera (commonly known as Swallow wort) is described in the Ayurvedic literature for the treatment of inflammation and arthritic disorders. Therefore, in the present work, the antiarthritic activity of potential fractions of Swallow wort leaf was evaluated and compared with standards (indomethacin and ibuprofen). This study was designed in Wistar rats for the investigation of antiarthritic activity and acute toxicity of Swallow wort. Arthritis was induced in Wistar rats by injecting 0.1 mL of Freund’s complete adjuvant (FCA) on the 1st and 7th days subcutaneously into the subplantar region of the left hind paw. Evaluation of our experimental findings suggested that antiarthritic activity of methanol fraction of Swallow wort (MFCP) was greater than ethyl acetate fraction of Swallow wort (EAFCP), equal to standard ibuprofen, and slightly lower than standard indomethacin. MFCP significantly reduced paw edema on the 17th, 21st, 24th, and 28th days. It also showed significant effect (p < 0.01) on arthritic score, paw withdrawal latency, and body weight. The inhibition of serum lysosomal enzymes and proinflammatory cytokines along with improvement of radiographic features of hind legs was also recorded with MFCP. Finally, it was concluded that MFCP can be a feasible therapeutic candidate for the treatment of inflammatory arthritis

Rapid, Sensitive, and Sustainable Reversed-Phase HPTLC Method in Comparison to the Normal-Phase HPTLC for the Determination of Pterostilbene in Capsule Dosage Form

The greenness evaluation of literature analytical methods for pterostilbene (PT) analysis was not performed. Accordingly, the rapid, sensitive, and green/sustainable reversed-phase high-performance thin-layer chromatography (RP-HPTLC) method was developed and compared to the normal-phase (NP)-HPTLC (NP-HPTLC) for the estimation of PT with a classical univariate calibration. The RP quantification of PT was performed using green solvent systems; however, the NP analysis of PT was performed using routine solvent systems. The PT was detected at 302 nm for both of the methods. The greenness scores for the current analytical assays were evaluated by the analytical GREEnness (AGREE) metric approach. The classical univariate calibration for RP and NP methods indicated the linearity range as 10–1600 and 30–400 ng band−1, respectively. The RP method was more reliable for PT analysis compared to the NP method. The PT contents in commercial capsule dosage form were found to be 100.84% using the RP method; however, the PT contents in commercial capsule dosage form were determined as 92.59% using the NP method. The AGREE scores for RP and NP methods were 0.78 and 0.46, respectively. The sustainable RP-HPTLC assay was able to detect PT in the presence of its degradation products, and hence it can be considered as a selective and stability-indicating method. Accordingly, the RP-HPTLC method with univariate calibration has been considered as a superior method over the NP-HPTLC method for PT analysis

Review on cerebral malaria—Pathogenesis and role of EphA2 receptor in maintaining blood brain barrier integrity

Plasmodium species causes cerebral malaria (CM), a dangerous parasitic illness. The World Health Organization estimates that there were roughly 228 million cases of malaria in 2018, which resulted in 405,000 tragic deaths. There was an approximate 20 % mortality rate among children diagnosed with CM who were admitted to the hospital. 67 % of the victims were children less than five years old. Patients who survive CM may experience lifetime post-CM complications and a higher risk of childhood neurodisability. The present review discuss about cellular mechanisms and immunological responses causing cerebral malaria. The breakdown of tight junctions and adherence junctions between endothelial cells (ECs) is the cause of an increase in the permeability of the blood brain barrier (BBB). It is obvious that this barrier can be breached by two different mechanisms: a) the apoptosis of ECs, and b) a loosening of the tight junctions between cells. T cells have been shown to have an important role in the development of cerebral malaria in an experimental mouse model (ECM). EphA2 receptors has been identified as contributing to many neurological illnesses and plays an important role in CM, associated with an impairment of the BBB. EphA2 is a key target protein that promotes EC apoptosis by targeting ephrin A ligand-expressing CD8+ T cell adhesion. Prominent role of the EphA2 receptors in CM has never been highlighted so far. Despite an intensive research, there is still a lack of successful malaria vaccines. The most advanced vaccines created so far, RTS,S/AS01 and R21/Matrix-M, focus on combating the early stages of the P. falciparum parasite. This review also discuss about the progress made for developing an effective vaccine for cerebral malaria

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy

Abstract Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV–Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti–O–Ti bond is identified by observing a peak between 400 and 800 cm−1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 μg/mL and standard (Vitamin C) IC50 is 87.62 μg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer

Addressing the resurgence of global monkeypox (Mpox) through advanced drug delivery platforms

Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology