The clinical application of kaempferol (KP), a promising anticancer flavonoid, is limited by its poor bioavailability, rapid metabolism, and inadequate tissue distribution. To overcome these limitations, KP-loaded nanoliposomes (KP-LNPs) were developed, and their anti-hepatocellular carcinoma (HCC) potential was investigated. KP-LNPs were formulated and characterized using Fourier-transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), zeta potential, and particle size analysis. The anti-HCC effects and cellular internalization of KP-LNPs were assessed in vitro using HepG2 cells. Additionally, ELISA was performed to evaluate the concentration changes related to the mitochondrial apoptotic proteins i/e-NOS, p53 and Caspase-3/9. The optimized KP-LNP formulation exhibited a uniform average particle size of 141.4 ± 1.12 nm, with a polydispersity index (PDI) of 0.141 ± 0.02 and a zeta potential of − 28.57 ± 0.47 mV, indicating good stability. TEM and AFM analyses confirmed a spherical morphology, while FTIR spectra showed no interactions between KP and the lipid components. The entrapment efficiency of KP was 83 Liposomes are potentially active hydrophobic and hydrophilic molecules because of their high biocompatibility, biodegradability, and minimal immunogenicity. Phosphatidylcholine, a zwitterionic and membrane-mimetic lipid, is commonly used owing to its stability and physiological compatibility. The anti-HCC effects of KP-LNPs were assessed using HepG2 cells. KP-LNPs induced apoptosis through the i/e-NOS/p53/Caspase-mediated apoptotic pathway.

Exosomes are intrinsic membrane-based vesicles that play a key role in both normal and pathological processes. Since their discovery, exosomes have been investigated as viable drug delivery systems and clinical indicators because of their magnitude and effectiveness in delivering biological components to targeted cells. Exosome characteristics are biocompatible, prefer tumor recruitment, have tunable targeting efficiency, and are stable, making them outstanding and eye-catching medication delivery systems for cancer and other disorders. There is great interest in using cell-released tiny vesicles that activate the immune system in the age of the fast development of cancer immunotherapy. Exosomes, which are cell-derived nanovesicles, have a lot of potential for application in cancer immunotherapy due to their immunogenicity and molecular transfer function. More significantly, exosomes can transfer their cargo to specified cells and so affect the phenotypic and immune-regulation capabilities of those cells. In this article, we summarize exosomes' biogenesis, isolation techniques, drug delivery, applications, and recent clinical updates. The use of exosomes as drug-delivery systems for small compounds, macromolecules, and nucleotides has recently advanced. We have tried to give holistic and exhaustive pieces of information showcasing current progress and clinical updates of exosomes.

We have performed a comprehensive numerical and analytical examination of two crucial transport aspects in silicene: the phonon-drag thermopower, S p , and the electron's energy loss rate, F e . Specifically, our investigation is centered on their responses to out-of-plane flexural phonons and in-plane acoustic phonons in silicene, a two-dimensional allotrope of silicon as a function of electron temperature, T , and electron concentration, n , upto the room temperature. It is found that the calculated quantities have a non-monotonic dependence for the phonon modes for both parameters ( T and n ) considered while analytical results predict definite dependencies up to the complete low-temperature Bloch-Gruneisen (BG) regime. To provide a more comprehensive picture, we contrast the complete numerical outcomes with the approximated analytical BG results, revealing a convergence within a specific range of temperature and carrier concentration. In light of this convergence, we put forth suggestions to elucidate the underlying factors responsible for this behavior. A comparison based on the magnitude of the calculated quantities can be made from the figures between the two considered phonon modes, which clearly shows that the out-of-plane flexural phonons are effective throughout the considered temperature range. This observation leads us to posit that the dominating contribution of the out-of-plane flexural phonon modes hinges upon the deformation potential constant and phonon energy associated with the phonon mode. Our study carries significant implications for estimating the electrical and thermal properties of silicene and provides valuable insights for the development of devices based on silicene-based technologies.

The utilization of large language models (LLMs) has become a significant advancement in the domains of medicine and clinical informatics, providing a revolutionary potential for scientific breakthroughs and customized therapies. LLM models are trained on large datasets and exhibit the capacity to comprehend and analyze intricate biological data, encompassing genomic sequences, protein structures, and clinical health records. With the utilization of their comprehension of the language of biology, they possess the ability to reveal concealed patterns and insights that may evade human researchers. LLMs have been shown to positively impact various aspects of molecular biology, including the following: genomic analysis, drug development, precision medicine, biomarker development, experimental design, collaborative research, and accessibility to specialized expertise. However, it is imperative to acknowledge and tackle the obstacles and ethical implications involved. The careful consideration of data bias and generalization, data privacy and security, explainability and interpretability, and ethical concerns around responsible application is vital. The successful resolution of these obstacles will enable us to fully utilize the capabilities of LLMs, leading to substantial progress in the fields of molecular biology and pharmaceutical research. This progression also has the ability to bolster influential impacts for both the individual and the broader community.

Objective:To extract and isolate berberine from Berberis aristata(Berberidaceae).Isolated berberine was characterised using spectroscopy and its antioxidant and antiarthritic activity was analyzed. Methods:The berberine was isolated from B.aristata using microwave-assisted extraction(MAE)and characterised by a spectroscopic technique.The isolated berberine was evaluated for its antioxidant activity in DPPH,nitric oxide,and superoxide scavenging assays,while antiarthritic activity was evalu-ated in the complete freund's adjuvant(CFA)-induced arthritis rat model. Results:The antioxidant activity of berberine revealed potent antioxidant activity in DPPH,nitric oxide,and superoxide scavenging assays.The in vivo antiarthritic activity of berberine in the CFA-induced arthritis rat model showed a significant reduction in paw diameter,arthritic score,and an increase in body weight.Furthermore,a concentration-dependent ameliorating action of berberine on haematolog-ical parameters was noticed.Proinflammatory biomarkers,including IL-6,IL-10,and TGF-b in serum were reported,and histopathology examination revealed that berberine decreased pannus formation,synovial hyperplasia,and bone erosion.Radiographic investigation showed soft tissue inflammation,bone resorp-tion and erosion,joint gap reduction,and substantial connective tissue expansion after treatment with berberine. Conclusion:The ameliorating action on haematological parameters and proinflammatory biomarkers of berberine makes them a suitable remedy for the treatment of arthritis.

The study was performed to identify the imperative pharmacognostic details of berberis aristata DC roots. The root of the plant was standardized by morphologically and microscopically. Further other parameters chemomicroscopical, physical, hytochemical screening and florescence analysis were performed to determine the diagnostic features of berberis aristata DC (B. aristata). Macro and microscopic studies were also reported in the present study. Physicochemical parameters including extractive values, ash values, moisture content have been calculated, which showed 0.79 total ash, 0.05 acid insoluble ash, 20 water soluble ash and 0.90 water insoluble ash. The extractive values of berberis aristata DC were found to be 3.6, 1.2, 0.6 and 2.3 in ethanol, Pet. ether, acetone, and in water respectively. Phytochemical analysis closely revealed the presence of alkaloids in this plant. These outcomes will further help to standardize, identification and in execution research on this plant.

: The lack of currently available drugs for treating diabetes complications has stimulated our interest in finding new Aldose Reductase inhibitors (ARIs) with more beneficial biological properties. One metabolic method uses aldose reductase inhibitors in the first step of the polyol pathway to control excess glucose flux in diabetic tissues. Computer-aided drug discovery (CADD) is key in finding and optimizing potential lead substances. AR inhibitors (ARI) have been widely discussed in the literature. For example, Epalrestat is currently the only ARI used to treat patients with diabetic neuropathy in Japan, India, and China. Inhibiting R in patients with severe to moderate diabetic autonomic neuropathy benefits heart rate variability. AT-001, an AR inhibitor, is now being tested in COVID-19 to see how safe and effective it reduces inflammation and cardiac damage. In summary, these results from animal and human studies strongly indicate that AR can cause cardiovascular complications in diabetes. The current multi-center, large-scale randomized human study of the newly developed powerful ARI may prove its role in diabetic cardiovascular disease to establish therapeutic potential. During the recent coronavirus disease (COVID-19) outbreak in 2019, diabetes and cardiovascular disease were risk factors for severely negative clinical outcomes in patients with COVID19. New data shows that diabetes and obesity are among the strongest predictors of COVID-19 hospitalization. Patients and risk factors for severe morbidity and mortality of COVID- 19.

Ni1-xLaxO (x = 0.00, 0.01, and 0.03) nanostructures have been synthesized by the conventional sol-gel method, and further the electrical conduction and thermal stability have been investigated. It is observed that epsilon' decreases with increasing frequency and does not exhibit any significant change with temperature T < 150 degrees C. It attains a high value epsilon' similar to 10(3)-10(4) (75 kHz and 300 degrees C) for NiO sample. The high value of epsilon' in pure and LNO samples might be explained via electron relaxation-mode-coupling model, associated with oxygen vacancies (OVs) which become dominant at high temperature. The high-temperature dielectric relaxation behavior was also observed in all the samples. The calculated activation energies (U-cond and U-ac) from DC and AC conductivities, revealing that the relaxation behavior associated with the migration of OVs as confirmed by the EPR spectroscopy. On the other hand, a highly doped (x = 0.03) LNO sample shows high thermal stability than pure NiO, which needs a much higher degradation temperature, i.e., above 500 degrees C. The thermal activation energy was also determined in the temperature range of 80-150 degrees C.

•Berberine-loaded invasomes were prepared by thin film hydration method.•Prepared invasomes were characterized and determined their skin permeation studies.•Furthermore, berberine-loaded invasomal gel was formulated with 2% carbopol for transdermal delivery.•Prepared gel was evaluated for haematological factors, proinflammatory biomarkers and radiographical analysis in CFA-induced albino rat model.•Additionally, analgesic and anti-arthritic activity of prepared gel was determined in CFA-induced arthritis rat model.

A rising amount of research demonstrates that artificial intelligence and machine learning approaches can provide an essential basis for the drug design and discovery process. Deep learning algorithms are being developed in response to recent advances in computer technology as part of the creation of therapeutically relevant medications for the treatment of a variety of ailments. In this review, we focus on the most recent advances in the areas of drug design and discovery research employing generative deep learning methodologies such as generative adversarial network (GAN) frameworks. To begin, we examine drug design and discovery studies that use several GAN methodologies to evaluate one key application, such as molecular de novo design in drug design and discovery. Furthermore, we discuss many GAN models for dimension reduction of single-cell data at the preclinical stage of the drug development pipeline. We also show various experiments in de novo peptide and protein creation utilizing GAN frameworks. Furthermore, we discuss the limits of past drug design and discovery research employing GAN models. Finally, we give a discussion on future research prospects and obstacles.

The issue of emerging resistance to antitubercular drugs has created a formidable barrier in the effective prevention and cure of tuberculosis globally. In an effort to search for new antimycobacterial agents, possibly comprising new pharmacophore, novel triazole-isatin derivatives were designed as Mycobacterium tuberculosis shikimate kinase inhibitors and synthesized by microwave-assisted method. The synthesized molecules were evaluated for their antimycobacterial activity by MABA assay against M. tuberculosis H37Rv. The molecule 5h demonstrated MIC of 0.8 μg/ml and good safety profile with higher selectivity index with HEK293 cell line. The antimycobacterial activity was further substantiated with molecular docking studies. The triazole-isatin derivatives showed significant binding interactions with amino acid residues in the active site of the enzyme. These studies revealed that molecule 5h could act as a potential lead molecule for further studies to find new target-directed molecules.

Vesicular drug delivery systems are fascinating carriers utilizes for drug targeting to improve their therapeutic efficacy. These vesicular systems, deliver the drugs at predetermined rate by controlling and sustaining release as per the requirement. Invasomes, liposomes, ethosomes, niosomes, transferosomes, pharmacosomes, colloidosomes, herbosomes and sphinosomes are the numerous vesicular drug delivery systems especially utilizes for transdermal drug delivery. Although these vesicular drug delivery systems have been explored extensively, however, literature on invasomes is relatively scanty. The present write up describe numerous aspects of invasomes including structural features, composition and skin penetration mechanism. Ethanol, terpenes and phospholipids are the key structural composition, systematize physicochemical properties of invasomes. Furthermore, invasomes applications in the treatment of hypertension, acne, cancer, eosinophilic pustular folliculitis, erectile dysfunction and photodynamic therapy have also been discussed. Although invasomes possess potential advantages for transdermal drug delivery, however the stability of invasome limits its value.

The objectives of current work were to develop chitosan microparticles loaded controlled release floating gas generating minitablets of captopril. Chitosan microparticles were developed using ionic gelation method by dropping sodium tripolyphosphate solution into chitosan solution under stirring. Primary formulation variables were screened by applying Plackett Burman design and levels of most significant risk factors were optimized using 3(2) factorial design. Primary formulation variables were chitosan concentration (X1), sodium tripolyphosphate concentration (X2) and speed of stirring. Optimized batch of microparticle has particle size of 346.9 nm, zeta potential of 9.16 mv and drug release of 96% in simulated gastric fluid at the end of 8 h. Further microparticle loaded minitablets were developed and optimized. Microparticle loaded minitablets are characterized for parameters like dissolution, floating lag time, total floating time etc. Stability study of the optimized batch was carried out at 40 degrees C/75% RH for 6 months and at 30 degrees C/5% RH for 1 year. In vivo behaviour of optimized tablets was studied in rabbits with the help of X-ray studies. Optimized formulations were retained and floating in the gastric region for more than 24hrs. Bioavailability study confirms prolonged drug release.

Nanocrystalline orthochromatic perovskite structured La1- xEuxCrO3 (x = 0.0, 0.01, 0.03 and 0.05) compounds have been prepared via a solid-state reaction method calcined at a temperature 1200 degrees C. Here, we investigate the influence of Eu3+ on the structural, optical and magnetic properties of orthorhombic perovskite structured pure and doped LaCrO3 (LCO) samples with the help of surface characterizations such as SEM and XPS. Orthorhombic Pbnm structure and single-phase nature have been confirmed by the Reitveld refinement of X-ray diffraction data in all the samples. Predominantly, an optical gap of 3.81 eV has been produced experimentally, which is in good agreement with charge transfer (CT) gap and hence, explains the red color of Eu3+ doped LCO compounds. The study of the crystallographic data revealed a strong correlation between structural and magnetic properties. For instance, intrinsic structural distortion facilitates valance charge transfer (VCT) to the empty e component of the hybridized orbital, i.e., t(2g)(3) - O - e(0) and leads to observed weak ferromagnetism (WFM) coupling in anti-ferromagnetic LCO and doped LCO compounds. (C) 2020 Elsevier B.V. All rights reserved.

Background: The major issues with anticancer agent are that they randomly attack cancerous as well as healthy cell. These are injurious and its side effects can be reduced by developing a drug delivery vehicle. That is particular to tumor cells and this may be achieved by employing a strategy called active targeting strategy wherein the functionalities that respond to over expressed receptors (e.g., biotin, and folate conjunction on dendrimers surface) on tumor cells are attached to the drug carrier. Objective: In the present study, biotin- G4 PAMAM dendrimer conjugates were synthesized and structures were characterized. Materials and Methods: G4 -PAMAM Dendrimers were biotinylated using sulfo-NHS-LC-biotin and structural characterization was performed using 1 H NMR and transmission electron microscopy. The effect of generation and release rate, hemotoxicity with biotinylated dendrimer was performed. Results: The results suggested that biotinylated G4 PAMAM dendrimers may be potential drug carriers for paclitaxel targeting to cancer. Conclusion: Biotinylated G4 -PAMAM dendrimers show potential as nanocarriers in targeted drug delivery. Biotinylation of dendrimer thus reduces the distracted charge-mediated uptake and as well as also rising the in vivo biocompatibility, as seen with decrease in hemotoxicity with biotinylated dendrimers.

Many efforts have been made to introduce room-temperature ferromagnetism (RTFM) in metal oxide semiconductors doped with either magnetic or nonmagnetic ions for their suitable application in spintronics in the past few years. However, it is not yet well understood whether the origin of RTFM in these systems is intrinsic or because of magnetic clusters. Hence, we report detailed experimental investigations on RTFM in Nd-doped SnO2 nanostructures synthesized using a sol-gel process, which has potential spintronics application. In the present work, we observe that defects/oxygen vacancies play a crucial role in improving the RTFM in SnO2 doped with Nd ions. The presence of oxygen vacancies in the prepared samples was confirmed by Raman scattering, X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) spectroscopy. The enhancement of the density of oxygen vacancies was further quantified by the deconvoluted core-level O 1s XPS spectra. All samples exhibited RTFM with a small contribution of paramagnetic (PM) ordering. These phases (FM + PM) were established by fitting all M-H curves using a two-phase theoretical model. Furthermore, the Curie-Weiss and spin wave (CWSW) model fitted the M-T curve well, which also indicated the existence of the two phases in our systems. The overlapping of bound magnetic polarons occurred because of the exchange interaction between Nd3+ ions and electrons trapped in oxygen vacancies; this overlap is responsible for introducing RTFM in Nd-doped SnO2. Hence, the origin of RTFM can be mostly explained by the bound magnetic polaron (BMP) model.

During the last decade, room temperature ferromagnetism (RTFM) has been observed in doped transition metal oxides (TMOs) such as NiO. However, the origin of RTFM is not clearly understood and to date, it is highly debated. Here, we have investigated the origin of RTFM in nonmagnetic ion doped NiO, and consider the cubic structured La-doped NiO for this purpose. Single phase cubic structure of prepared samples revealed the absence of magnetic ion cluster and all the samples exhibit intrinsic cause of RTFM. Also, to address the only intrinsic reason of magnetism, we avoid the magnetic ion doping in NiO. By analysing the X ray diffraction (XRD), Raman analysis, photoluminescence (PL) and X-ray photoelectron spectroscopy (XPS), the essential features of RTFM in doped NiO are found as: (i) almost hysteretic and temperature-independent magnetization (ii) non zero and high value of coercive field at high concentration of La (x = 0.05) that confirms the long-range ferromagnetism in doped NiO (iii) the saturation magnetization achieves a high value of 10.101 emu/g for La content (x = 0.01) confirming a sensation for saturation magnetization at this La content. These features demonstrate the RTFM in doped NiO are due to overlapped bound magnetic polarons (BMPs) created by the exchange interaction between the spin of La3+ ion and spin of the localized hole due to F center. Based on experimental and theoretical observations, it is suggested that the particular oxygen vacancy mediated exchange interaction between La3+-La3+ ions at higher concentration of La (x = 0.05) is responsible for the RTFM in doped NiO. (C) 2020 Elsevier B.V. All rights reserved.

In this report, we have synthesized Ni0.98Pb0.02O nanoparticles using a chemical route such as sol-gel method. With the help of X-ray diffractometer (XRD) and scanning electron microscope (SEM), it is observed that nanoparticles are single-phase and spherical shaped with the crystallite size calculated using both of Sherrer method (S-H) (6.57 nm) and William Hall method (W-H) (10.19 nm). In addition to this, the optical band energy (3.65 eV) has been estimated using the Tauc model with associated Urbach energy (170 meV) and this low value of Urbach energyconfirms the less induced disorder with Pb doping. By the photoluminescence spectroscopy, we report the effect of intrinsic defects (nickel vacancies in the surface, oxygen vacancies and oxygen interstitial etc.) on the bandgap of NiO nanoparticles in terms of many visible emissions (Blue, Green and Orange) which make the Pb doped NiO as visible light emitter.

Despite poor bioavailability of the drug and in vivo stability, curcumin has been reported for many pharmacological activities. Considering the potential of dendrimers as a drug delivery system, current research work is focused on the formulation and characterization of G4 PAMAM dendrimer-Palmitic acid core-shell nanoparticle-containing curcumin as antistress therapeutics to maximize the bioavailability of curcumin. Various formulations were prepared using different concentrations of palmitic acid and an optimized ratio of dendrimer and curcumin. All formulations were investigated for evaluation of physicochemical parameters, encapsulation efficiency, and in vitro release. Particle size, PDI, zeta-potential, and encapsulation efficiency of final formulation was found to be 257.9 +/- 0.365 nm, 0.10 +/- 0.004, 3.59 +/- 0.167 mV, and 80.87%, respectively. In vitro release studies have shown that 53.62 +/- 2.431% of the drug was released after 24 h. In vivo studies pharmacokinetic parameters, drug distribution, pharmacological, and toxicological were also estimated using swiss albino mice. The findings have shown the selected formulation is better than plain curcumin formulation.