Unraveling the role of cloud computing in health care system and biomedical sciences.

Cloud computing has emerged as a transformative force in healthcare and biomedical sciences, offering scalable, on-demand resources for managing vast amounts of data. This review explores the integration of cloud computing within these fields, highlighting its pivotal role in enhancing data management, security, and accessibility. We examine the application of cloud computing in various healthcare domains, including electronic medical records, telemedicine, and personalized patient care, as well as its impact on bioinformatics research, particularly in genomics, proteomics, and metabolomics. The review also addresses the challenges and ethical considerations associated with cloud-based healthcare solutions, such as data privacy and cybersecurity. By providing a comprehensive overview, we aim to assist readers in understanding the significance of cloud computing in modern medical applications and its potential to revolutionize both patient care and biomedical research.

BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aß) and tau accumulation. Aß accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aß accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aß pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

Identification of novel c-Kit inhibitors from natural sources using virtual screening and molecular dynamics simulations.

The Mast/Stem cell growth factor receptor Kit (c-Kit), a Proto-oncogene c-Kit, is a tyrosine-protein kinase involved in cell differentiation, proliferation, migration, and survival. Its role in developing certain cancers, particularly gastrointestinal stromal tumors (GISTs) and acute myeloid leukemia (AML), makes it an attractive therapeutic target. Several small molecule inhibitors targeting c-Kit have been developed and approved for clinical use. Recent studies have focused on identifying and optimizing natural compounds as c-Kit inhibitors employing virtual screening. Still, drug resistance, off-target side effects, and variability in patient response remain significant challenges. From this perspective, phytochemicals could be an important resource for discovering novel c-Kit inhibitors with less toxicity, improved efficacy, and high specificity. This study aimed to uncover possible c-Kit inhibitors by utilizing a structure-based virtual screening of active phytoconstituents from Indian medicinal plants. Through the screening stages, two promising candidates, Anilinonaphthalene and Licoflavonol, were chosen based on their drug-like features and ability to bind to c-Kit. These chosen candidates were subjected to all-atom molecular dynamics (MD) simulations to evaluate their stability and interaction with c-Kit. The selected compounds Anilinonaphthalene from Daucus carota and Licoflavonol from Glycyrrhiza glabra showed their potential to act as selective binding partners of c-Kit. Our results suggest that the identified phytoconstituents could serve as a starting point to develop novel c-Kit inhibitors for developing new and effective therapies against multiple cancers, including GISTs and AML. The use of virtual screening and MD simulations provides a rational approach to discovering potential drug candidates from natural sources.Communicated by Ramaswamy H. Sarma.

Causal Association Between Anemia and Cardiovascular Disease: A 2-Sample Bidirectional Mendelian Randomization Study.

Background Although previous observational studies have shown an association between anemia and cardiovascular disease (CVD), the underlying causal relationship between anemia and CVD remains uncertain. Methods and Results We conducted a 2-sample bidirectional Mendelian randomization (MR) study to assess the causal association between anemia and CVD. We extracted summary statistics data for anemia, heart failure (HF), coronary artery disease (CAD), atrial fibrillation, any stroke, and any ischemic stroke (AIS) from relevant published genome-wide association studies. After rigorous quality control steps, independent single-nucleotide polymorphisms for each disease were selected as instrumental variables. Inverse-variance weighting was used as the primary method to estimate the causal association between anemia and CVD in the 2-sample MR analysis. Simultaneously, we performed a series of multiple methods analyses (median weighting, maximum likelihood [MR robust adjusted profile score]), sensitivity analyses (Cochran's Q test and MR-Egger intercept, leave-one-out test [MR pleiotropy residual sum and outlier]), instrumental variable strength evaluations (F statistic), and statistic power estimates to verify the robustness and reliability of our results. Furthermore, the associations between anemia and CVD from different studies, including the UK Biobank and FinnGen studies, were combined by meta-analysis. The MR analysis showed that genetically predicted anemia was significantly associated with HF risk at the Bonferroni-corrected significance level (odds ratio [OR], 1.11 [95% CI, 1.04-1.18]; P=0.002) and was suggestively associated with CAD risk (OR, 1.11 [95% CI, 1.02-1.22]; P=0.020). However, the associations between anemia and atrial fibrillation, any stroke, or AIS were not statistically significant. In the reverse MR analysis, we found that genetic susceptibility to HF, CAD, and AIS was significantly associated with anemia risk. The ORs of HF, CAD, and AIS were 1.64 (95% CI, 1.39-1.94; P=7.60E-09), 1.16 (95% CI, 1.08-1.24; P=2.32E-05), and 1.30 (95% CI, 1.11-1.52; P=0.001), respectively. Genetically predicted atrial fibrillation was suggestively associated with anemia (OR, 1.06 [95% CI, 1.01-1.12]; P=0.015). Sensitivity analyses found weak evidence of horizontal pleiotropy and heterogeneity, which ensured the robustness and reliability of the results. Meta-analysis also showed the statistically significant association between anemia and HF risk. Conclusions Our study supports bidirectional causality between anemia and HF and significant associations between genetic predisposition to CAD and AIS with anemia, which contributes to the clinical management of both diseases.

Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis.

Background: Atrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism and analyze immune infiltration in DCM complicated with AF through comprehensive bioinformatics analysis. Methods: The gene expression datasets of DCM (GSE141910) and AF (GSE41177 and GSE79768) were obtained from the Gene Expression Omnibus database. Gene enrichment analyses were performed after screening the common differentially expressed genes (DEGs) of DCM and AF. Protein-protein interaction network was constructed in the STRING database and visualized in Cytoscape software, which helped to further screen the central functional modules of DEGs and hub genes. In addition, ImmuCellAI algorithm was performed to estimate immune infiltration patterns, and Spearman correlation was conducted to investigate the correlation between the abundance of multiple immune cells and the expression levels of hub immune-related genes after obtaining hub immune-related genes from the ImmPort database. The hub immune-related genes expression and immune infiltration patterns were additionally verified in the validation datasets (GSE57338, GSE115574, and GSE31821). The diagnostic effectiveness of hub immune-related genes was evaluated through Receiver Operator Characteristic Curve analysis. Results: A total of 184 common DEGs in DCM and AF were identified for subsequent analyses. The functions of hub genes were significantly associated with immune responses. We identified 7 hub immune-related genes (HLA-DRA, LCK, ITK, CD48, CD247, CD3D, and IL2RG) and a spectrum of immune cell subsets including Monocyte, Neutrophil, and follicular helper T (Tfh) cells were found to be concurrently dysregulated in both DCM and AF. 7 hub immune-related genes were predominantly favorably correlated with Tfh cells and were primarily negatively correlated with Neutrophil infiltrations in DCM and AF. CD48+CD3D were verified to diagnose DCM and AF with excellent sensitivity and specificity, showing favorable diagnostic value. Conclusions: Our study reveals that immune cells (Tfh cells) disorders caused by hub immune-related genes (CD48 and CD3D) may be the common pathogenesis of DCM combined with AF, which lays a foundation for further immune mechanism research.

Elucidating the Neuroprotective Effect of Tecoma stans Leaf Extract in STZ-Induced Diabetic Neuropathy.

Background: Diabetes is considered one of the most encyclopedic metabolic disorders owing to an alarming rise in the number of patients, which is increasing at an exponential rate. With the current therapeutics, which only aims to provide symptomatic and momentary relief, the scientists are shifting gears to explore alternative therapies which not only can target diabetes but can also help in limiting the progression of diabetic complications including diabetic neuropathy (DN). Methods: Tecoma stans leaf methanolic extract was prepared using the Soxhlet method. A streptozotocin (STZ; 45 mg/kg)-induced diabetic animal model was used and treatment with oral dosing of T. stans leaf extract at the different doses of 200 mg/kg, 300 mg/kg, and highest dose, i.e., 400 mg/kg, was initiated on day 3 after STZ administration. The pharmacological response for general and biochemical (angiogenic, inflammatory, and oxidative) parameters and behavioral parameters were compared using Gabapentin as a standard drug with the results from the test drug. Results: Parameters associated with the pathogenesis of diabetic neuropathy were evaluated. For general parameters, different doses of T. stans extract (TSE) on blood sugar showed significant effects as compared to the diabetic group. Also, the results from biochemical analysis and behavioral parameters showed significant positive effects in line with general parameters. The combination therapy of TSE at 400 mg/kg with a standard drug produced nonsignificant effects in comparison with the normal group. Conclusion: The leaves of T. stans possess antidiabetic effects along with promising effects in the management of DN by producing significant effects by exhibiting antioxidative, antiangiogenic, and anti-inflammatory properties, which are prognostic markers for DN, and thus, T. stans can be considered as an emerging therapeutic option for DN.

Effects of NO modulators and antioxidants on endocrine and cellular markers in rats under repetitive restraint stress.

The aim of the study was to evaluate the effects of NO modulators and antioxidant treatments on endocrine (plasma corticosterone), cellular (heat shock protein 70 [HSP-70] and nuclear factor κB [NF-κB]), and oxidative stress markers in repetitively stressed rats. Repetitive (restraint) stress (RS 1hr/day × 21 days) enhanced the levels of cellular and endocrine stress markers in the rat blood and altered pro-oxidant-antioxidant balance differentially in the control and test groups. Exposure to repetitive RS enhanced malondialdehyde (MDA) levels, lowered reduced glutathione (GSH), and superoxide dismutase (SOD) levels as well as nitric oxide (NOx) levels. NO precursor L-arginine and NO synthase inhibitors were found to differentially modulate stress-induced mechanism in altering NF-κB, HSP-70, and corticosterone levels. The antioxidant L-ascorbic acid (L-AA) significantly suppressed RS(×21)-induced elevation of NF-κB and HSP-70 levels, depicting protective effects, as also evidenced by reversal of elevated corticosterone levels. The results suggest that NO modulators and antioxidants differentially influence repetitive stress-induced changes in endocrine and cellular markers, and the complex interaction between NO and cellular markers like HSP70 and NF-κB plays a crucial modulatory role in this phenomenon.

Probing pH sensitivity of αC-phycoerythrin and its natural truncant: A comparative study.

Cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue exists in two natural forms named as full length (FL-αC-PE) and truncated (Tr-αC-PE). FL-αC-PE and Tr-αC-PE are produced when cyanobacterium is grown in the optimal medium and nutrient deficient medium, respectively. Despite of N-terminal deletion, both proteins show similar spectroscopic properties. In this study, different optical properties of these two natural variants of C-PE were measured in the pH range 1.0-12.0 (1.0 ≤ pH ≤ 12.0). It was observed that: (i) their absorption, fluorescence and CD spectra remain unchanged within the range adjacent to neutral pH, 5.5-8.75, (ii) at pH values higher than 8.75 and lower than 5.5 their absorption, fluorescence and CD spectral signatures are changed significantly, and (iii) emission spectra of the covalently linked tetrapyrrole chromophores and Trp residue are perturbed at extreme pH values in the range 8.75

Role of N-terminal residues on folding and stability of C-phycoerythrin: simulation and urea-induced denaturation studies.

The conformational state of biliproteins can be determined by optical properties of the covalently linked chromophores. Recently determined crystal structure of truncated form of α-subunit of cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue provides a new insight into the structure-function relationship of αC-PE. To compare their stabilities, we have measured urea-induced denaturation transitions of the full length αC-PE (FL-αC-PE) and truncated αC-PE (Tr-αC-PE) followed by observing changes in absorbance at 565 nm, fluorescence at 350 and 573 nm, and circular dichroism at 222 nm as a function of [urea], the molar concentration of urea. The transition curve of each protein was analyzed for ΔG(D)(0), the value of Gibbs free energy change on denaturation (ΔG(D)) in the absence of urea; m, the slope (=∂∆G(D)/∂[urea]), and C(m), the midpoint of the denaturation curve, i.e. [urea] at which ΔG(D) = 0. A difference of about 10% in ΔG(D)(0) observed between FL-αC-PE and Tr-αC-PE, suggests that the two proteins are almost equally stable, and the natural deletion of 31 residues from the N-terminal side of the full length protein does not alter its stability. Furthermore, normalization of probes shows that the urea-induced denaturation of both the proteins is a two-state process. Folding of both structural variants (Tr-αC-PE and FL-αC-PE) of P. tenue were also studied using molecular dynamics simulations at 300 K. The results show clearly that the stability of the proteins is evenly distributed over the whole structure indicating no significant role of N-terminal residues in the stability of both proteins.

Folding and stability studies on C-PE and its natural N-terminal truncant.

The conformational and functional state of biliproteins can be determined by optical properties of the covalently linked chromophores. α-Subunit of most of the phycoerythrin contains 164 residues. Recently determined crystal structure of the naturally truncated form of α-subunit of cyanobacterial phycoerythrin (Tr-αC-PE) lacks 31 N-terminal residues present in its full length form (FL-αC-PE). This provides an opportunity to investigate the structure-function relationship between these two natural forms. We measured guanidinium chloride (GdmCl)-induced denaturation curves of FL-αC-PE and Tr-αC-PE proteins, followed by observing changes in absorbance at 565nm, fluorescence at 350 and 573nm, and circular dichroism at 222nm. The denaturation curve of each protein was analyzed for ΔGD(∘), the value of Gibbs free energy change on denaturation (ΔGD) in the absence of GdmCl. The main conclusions of the this study are: (i) GdmCl-induced denaturation (native state↔denatured state) of FL-αC-PE and Tr-αC-PE is reversible and follows a two-state mechanism, (ii) FL-αC-PE is 1.4kcalmol(-1) more stable than Tr-αC-PE, (iii) truncation of 31-residue long fragment that contains two α-helices, does not alter the 3-D structure of the remaining protein polypeptide chain, protein-chromophore interaction, and (iv) amino acid sequence of Tr-αC-PE determines the functional structure of the phycoerythrin.

Advancement in carbon nanotubes: basics, biomedical applications and toxicity.

OBJECTIVES: Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites. KEY FINDINGS: CNTs have been employed in the development of molecular electronic, composite materials and others due to their unique atomic structure, high surface area-to-volume ratio and excellent electronic, mechanical and thermal properties. Recently they have been exploited as novel nanocarriers in drug delivery systems and biomedical applications. Their larger inner volume as compared with the dimensions of the tube and easy immobilization of their outer surface with biocompatible materials make CNTs a superior nanomaterial for drug delivery. Literature reveals that CNTs are versatile carriers for controlled and targeted drug delivery, especially for cancer cells, because of their cell membrane penetrability. SUMMARY: This review enlightens the biomedical application of CNTs with special emphasis on utilization in controlled and targeted drug delivery, as a diagnostics tool and other possible uses in therapeutic systems. The review also focuses on the toxicity aspects of CNTs, and revealed that genotoxic potential, mutagenic and carcinogenic effects of different types of CNTs must be explored and overcome by formulating safe biomaterial for drug delivery. The review also describes the regulatory aspects and clinical and market status of CNTs.