Designing Pathway-Controlled Multicomponent Ultrashort Peptide Hydrogels with Diverse Functionalities at the Nanoscale for Directing Cellular Behavior.

Tuning self-assembling pathways by implementing different external stimuli has been extensively studied, owing to their effective control over structural and mechanical properties. Consequently, multicomponent peptide hydrogels with high structural tunability and stimuli responsiveness are crucial in dictating cellular behavior. Herein, we have implemented both coassembly approach and pathway-dependent self-assembly to design nonequilibrium nanostructures to understand the thermodynamic and kinetic aspects of peptide self-assembly toward controlling cellular response. Our system involved an ultrashort peptide gelator and a hydrophilic surfactant which coassembled through different pathways, i.e., heat-cool and sonication methods with variable energy input. Interestingly, it was possible to access diverse structural and mechanical properties at the nanoscale in a single coassembled system. Further, the hydrophilic surfactant provided additional surface functionalities, thus creating an efficient hydrophilic matrix for cellular interaction. Such diverse functionalities in a single coassembled system could lead to the development of advanced scaffolds, with applications in various biomedical fields.

Creating a more strategic small molecule biophysical hit characterization workflow.

To confirm target engagement of hits from our high-throughput screening efforts, we ran biophysical assays on several hundreds of hits from 15 different high-throughput screening campaigns. Analyzing the biophysical assay results from these screening campaigns led us to conclude that we could be more strategic in our biophysical analysis of hits by first confirming activity in a thermal shift assay (TSA) and then confirming activity in either a surface plasmon resonance (SPR) assay or a temperature-related intensity change (TRIC) assay. To understand how this new workflow shapes the quality of the final hits, we compared TSA/SPR or TSA/TRIC confirmed and unconfirmed hits to one another using four measures of compound quality: quantitative estimate of drug-likeness (QED), Pan-Assay Interference Compounds (PAINS), promiscuity, and aqueous solubility. In general, we found that the biophysically confirmed hits performed better in the compound quality metrics than the unconfirmed hits, demonstrating that our workflow not only confirmed target engagement of the hits but also enriched for higher quality hits.

Gene Polymorphism Influencing Persistent Bone Resorption in Brown Tumor: A Case Series with Possible Pathogenesis and Potential Therapeutic Approach.

Brown tumor represents a terminal stage of bone remodeling process due to an imbalance between osteoclastic and osteoblastic activity. It represents a reparative cellular process, rather than a neoplastic process mostly associated with primary or secondary hyperparathyroidism. Although parathyroidectomy is the first treatment of choice for brown tumors, several cases don't resolve even after normalization of parathyroid hormone levels which leads to surgical intervention. Therefore, to avoid multiple bone surgeries in the same patient, it is crucial to have a conservative approach like targeted therapy which could block certain molecules involved in bone resorption. In this string, we have recognized and quantified three molecules namely sclerostin, MCP-1 and CD73 in brown tumors and correlated their expression with bone resorption pathogenesis and potential therapeutic approach.

Perplexing First Branchialcleft Anomalies-A Case Series with Review of Literature.

Incomplete obliteration of the branchial apparatus results in the formation of branchial cleft anomalies. First branchial cleft anomalies may persist anywhere in the first branchial arch, from the external auditory canal at the level of the bony cartilaginous junction to the submandibular triangle. The majority of cases present in childhood as an opening in the skin though they may present as cysts or neck masses, mostly mistaken for neck abscesses which leads to inadequate treatment and complications. Here different cases of first branchial cleft anomalies with variable presentation and treatment are illustrated. The need for proper diagnosis and adequate treatment cannot be overemphasized to avoid mismanagement and complications.

Indium nanocubes based recyclable fluorescent chemosensor for sustainable environmental monitoring: pH-induced fluorescence transition and selective detection of Pd(II) ions.

Rapid modern industrialization and urbanization have escalated heavy metal pollution, with palladium (Pd2+) raising significant concerns due to its extensive usage in catalysis, hydrogen storage, and electronics, thereby imposing substantial risks on the environment and human health. In this study, we report a highly fluorescent indium nanocubes based chemosensor (InNCs) functionalized with perylene tetracarboxylic acid (PTCA) and 4-(pyridyl)ethenyl benzene (PEB). The InNCs exhibited emission maximum at 415 nm (λex âˆ¼ 350 nm) with robust chemical and photo-stability, and acted as a fluorogenic probe for selective recognition of Pd2+ in aqueous medium. The fluorescence sensing properties of InNCs were thoroughly assessed via different techniques including steady-state absorption, emission and time-resolved emission spectroscopic methods. Among the various competitive analytes, only Pd2+ could induce a significant fluorescence quenching in the probe. This "turn-off" fluorescence sensing demonstrated a remarkably low LoD of ∼65 nM. Notably, with the addition of EDTA, the probe displayed good recyclability upto 4 cycles. The sensory probe was successfully employed as a reusable platform to estimate Pd(II) in different real water and soil samples with considerable accuracy (∼ 5-10 % error). Moreover, the probe exhibited a pH-induced fluorescence transition, indicating its potential to be applied as a pH sensor. The Pd(II) binding and pH-sensing mechanisms have also been elucidated through density functional theory (DFT) calculations.

Evaluation of Diagnostic Efficacy of Novel Red Blood Cell Parameters as Potential Screening Test for Detecting Latent Iron Deficiency in Blood Donors.

Iron deficiency anemia (IDA) forms a major share of global burden of anemia. Frequent blood donation is a common iatrogenic cause of iron insufficiency in healthy adults. Serum iron and hemoglobin levels are normal despite low serum ferritin levels, referred to as latent iron deficiency (LID). Aim of the present study was to evaluate the role of novel RBC parameters-percentage of hypochromic RBCs (%HPO), percentage of microcytic RBCs (%MIC), and haemoglobin content of reticulocytes (MCHr) of Abbott Alinity autoanalyzer as indicators of latent iron deficiency in blood donors. 260 consenting and eligible blood donors were included in the study. Complete blood counts including new RBC parameters on Abbott Alinity autoanalyzer and serum iron profile were measured for all donors. Donors were categorized into LID and No LID based on Ferritin and Transferrin saturation (TSAT). Serum transferrin receptors (sTfR) were studied in a subset of samples [LID (n = 46), No LID (n = 18) and IDA (n = 27)]. Statistical analyses was done on IBM SPSS version 22. Among 260 donors, 56 (21.5%) were found to have LID. The difference in mean values for % HPO, % MIC, and MCHr were not found to be statistically significant in LID and No LID groups. sTfR results between LID, No LID and IDA sub-groups revealed significant difference. This study does not support the role of % HPO, % MIC and MCHr measured on Abott Alinity analyzer, as potential screening parameters for LID amongst blood donors. STfr was more informative in this regard. Further research on much larger sample size is required to confirm these findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01683-w.

Sesamol as a potent anticancer compound: from chemistry to cellular interactions.

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.

Integrative Modulation of Magnetic Resonance Transverse and Longitudinal Relaxivity in a Cell-Viable Bimagnetic Ensemble, γ-Fe2O3@ZnFe2O4.

The potential application of magnetic nanosystems as magnetic resonance imaging (MRI) contrast agents has been thoroughly investigated. This work seeks to attain robust MRI-contrast efficiency by designing an interacting landscape of a bimagnetic ensemble of zinc ferrite nanorods and maghemite nanoparticles, γ-Fe2O3@ZnFe2O4. Because of competing spin clusters and structural anisotropy triggered by isotropic γ-Fe2O3 and anisotropic ZnFe2O4, γ-Fe2O3@ZnFe2O4 undergoes the evolution of cluster spin-glass state as evident from the critical slowing down law. Such interacting γ-Fe2O3@ZnFe2O4 with spin flipping of 1.2 × 10-8 s and energy barrier of 8.2 × 10-14 erg reflects enhanced MRI-contrast signal. Additionally, γ-Fe2O3@ZnFe2O4 is cell-viable to noncancerous HEK 293 cell-line and shows no pro-tumorigenic activity as observed in MDA-MB-231, an extremely aggressive triple-negative breast cancer cell line. As a result, γ-Fe2O3@ZnFe2O4 is a feasible option for an MRI-contrast agent having longitudinal relaxivity, r1, of 0.46 s-1mM-1 and transverse relaxivity, r2, of 15.94 s-1mM-1, together with r2/r1 of 34.65 at 1.41 T up to a modest metal concentration of 0.1 mM. Hence, this study addresses an interacting isotropic/anisotropic framework with faster water proton decay in MR-relaxivity resulting in phantom signal amplification.

16S rRNA metagenomic profiling of red amaranth grown organically with different composts and soils.

In recent years organic food is gaining popularity as it is believed to promote better human health and improve soil sustainability, but there are apprehensions about pathogens in organic produces. This study was designed to understand the effect of different composts and soils on the status of the microbiome present in organically grown leafy vegetables. 16S rRNA metagenomic profiling of the leaves was done, and data were analyzed. It was found that by adding composts, the OTU of the microbiome in the organic produce was higher than in the conventional produce. The beneficial genera identified across the samples included plant growth promoters (Achromobacter, Paenibacillus, Pseudomonas, Sphingobacterium) and probiotics (Lactobacillus), which were higher in the organic produce. Some pathogenic genera, viz., plant pathogenic bacteria (Cellvibrio, Georgenia) and human pathogenic bacteria (Corynebacterium, Acinetobacter, Streptococcus, Streptomyces) were also found but with relatively low counts in the organic produce. Thus, the present study highlights that organic produce has lesser pathogen contamination than the conventional produce. KEY POINTS: • 16S rRNA metagenomics profiling done for organic red amaranth cultivar • Microbial richness varied with respect to the soil and compost type used • The ratio of beneficial to pathogenic genera improves with the addition of compost.

Enhancing sustainable crop cultivation: The impact of renewable soil amendments and digestate fertilizer on crop growth and nutrient composition.

Utilizing digestate as a fertilizer enhances soil nutrient content, improves fertility, and minimizes nutrient runoff, mitigating water pollution risks. This alternative approach replaces commercial fertilizers, thereby reducing their environmental impact and lowering greenhouse gas emissions associated with fertilizer production and landfilling. Herein, this study aimed to evaluate the impact of various soil amendments, including carbon fractions from waste materials (biochar, compost, and cocopeat), and food waste anaerobic digestate application methods on tomato plant growth (Solanum lycopersicum) and soil fertility. The results suggested that incorporating soil amendments (biochar, compost, and cocopeat) into the potting mix alongside digestate application significantly enhances crop yields, with increases ranging from 12.8 to 17.3% compared to treatments without digestate. Moreover, the combination of soil-biochar amendment and digestate application suggested notable improvements in nitrogen levels by 20.3% and phosphorus levels by 14%, surpassing the performance of the those without digestate. Microbial analysis revealed that the soil-biochar amendment significantly enhanced biological nitrification processes, leading to higher nitrogen levels compared to soil-compost and soil-cocopeat amendments, suggesting potential nitrogen availability enhancement within the rhizosphere's ecological system. Chlorophyll content analysis suggested a significant 6.91% increase with biochar and digestate inclusion in the soil, compared to the treatments without digestate. These findings underscore the substantial potential of crop cultivation using soil-biochar amendments in conjunction with organic fertilization through food waste anaerobic digestate, establishing a waste-to-food recycling system.

Investigation of RFC1 tandem nucleotide repeat locus in diverse neurodegenerative outcomes in an Indian cohort.

An intronic bi-allelic pentanucleotide repeat expansion mutation, (AAGGG)400-2000, at AAAAG repeat locus in RFC1 gene, is known as underlying genetic cause in cases with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and late-onset sporadic ataxia. Biallelic positive cases carry a common recessive risk haplotype, "AAGA," spanning RFC1 gene. In this study, our aim is to find prevalence of bi-allelic (AAGGG)exp in Indian ataxia and other neurological disorders and investigate the complexity of RFC1 repeat locus and its potential association with neurodegenerative diseases in Indian population-based cohorts. We carried out repeat number and repeat type estimation using flanking PCR and repeat primed PCR (AAAAG/AAAGG/AAGGG) in four Indian disease cohorts and healthy controls. Haplotype assessment of suspected cases was done by genotyping and confirmed by Sanger sequencing. Blood samples and consent of all the cases and detailed clinical details of positive cases were collected in collaboration with A.I.I.M.S. Furthermore, comprehension of RFC1 repeat locus and risk haplotype analysis in Indian background was performed on the NGS data of Indian healthy controls by ExpansionHunter, ExpansionHunter Denovo, and PHASE analysis, respectively. Genetic screening of RFC1-TNR locus in 1998 uncharacterized cases (SCA12: 87; uncharacterized ataxia: 1818, CMT: 93) and 564 heterogenous controls showed that the frequency of subjects with bi-allelic (AAGGG)exp are 1.15%, < 0.05%, 2.15%, and 0% respectively. Two RFC1 positive sporadic late-onset ataxia cases, one bi-allelic (AAGGG)exp and another, (AAAGG)~700/(AAGGG)exp, had recessive risk haplotype and CANVAS symptoms. Long normal alleles, 15-27, are significantly rare in ataxia cohort. In IndiGen control population (IndiGen; N = 1029), long normal repeat range, 15-27, is significantly associated with A3G3 and some rare repeat motifs, AGAGG, AACGG, AAGAG, and AAGGC. Risk-associated "AAGA" haplotype of the original pathogenic expansion of A2G3 was found associated with the A3G3 representing alleles in background population. Apart from bi-allelic (AAGGG)exp, we report cases with a new pathogenic expansion of (AAAGG)exp/(AAGGG)exp in RFC1 and recessive risk haplotype. We found different repeat motifs at RFC1 TNR locus, like AAAAG, AAAGG, AAAGGG, AAAAGG, AAGAG, AACGG, AAGGC, AGAGG, and AAGGG, in Indian background population except ACAGG and (AAAGG)n/(AAGGG)n. Our findings will help in further understanding the role of long normal repeat size and different repeat motifs, specifically AAAGG, AAAGGG, and other rare repeat motifs, at the RFC1 locus.

Concomitant Non-V600E BRAF and KRAS Mutations in Colorectal Carcinoma by Next-Generation Sequencing: A Distinct Subtype.

The RAS-RAF-MEK-ERK signaling cascade is the most frequently affected signaling pathway in colorectal cancer. BRAFV600E mutations serve as a drug-treatable hotspot and KRAS mutations as a predictor of susceptibility to anti-epidermal growth factor receptor therapy. Concomitant non-V600E BRAF and KRAS mutations may coexist and are rarely reported in the literature. We report a patient of colorectal carcinoma with inguinal lymph node metastases harboring mutations at the KRAS and BRAF non-V600E mutation codon detected by next-generation sequencing with an emphasis on clinical, pathological, and therapeutic implications of the mutation and review of the literature.

Designing Cardin-Motif Peptide and Heparin-Based Multicomponent Advanced Bioactive Hydrogel Scaffolds to Control Cellular Behavior.

Recently, peptide and sugar-based multicomponent systems have gained much interest in attaining the sophisticated structure and biofunctional complexity of the extracellular matrix (ECM). To this direction, we have designed for the first time a biologically relevant minimalist Cardin-motif peptide capable of binding ECM-derived glycosaminoglycans. Herein, we explored Cardin-motif peptide and heparin-based biomolecular matrix by employing simple noncovalent interactions at the molecular level. Interestingly, this peptide was inadequate to induce hydrogelation at ambient pH due to the presence of basic amino acids. However, addition of heparin successfully triggered its gelation at physiological pH following favorable electrostatic interactions with heparin. Importantly, the newly developed scaffolds displayed tunable nanofibrous morphology and superior mechanical properties as controlled simply by the differential mixing ratio of both biomolecular entities. Additionally, these composite scaffolds could closely mimic the complexity of ECM as they demonstrated superior biocompatibility and enhanced growth and proliferation of neural cells as compared to the peptide scaffold.

Role of HIF-1α in Ameloblastoma: A Systematic Review.

Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with unfavorable prognosis. Contemporary studies have proved its vital role in ameloblastoma by correlating its expression with the aggressiveness of the tumor. Therefore, an attempt was made to explore its significance in the malignant transformation and prognosis of ameloblastoma. The present systematic review aimed to understand the impact of HIF-1α in AMB which might lead to favorable outcomes in the treatment. An electronic search was carried out using PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles from all languages involving HIF-1α in AMB were scrutinized by two independent authors. Data were compiled and tabulated in Microsoft Excel and the Risk of bias was analyzed using the JBI tool. Twelve eligible articles were included for the quantitative analysis comprising 305 cases of AMB in which HIF-1α expression was studied for various characteristics like pattern, intensity, and site of immunoexpression which were found to be increased with an increase in the aggressiveness of AMB. It was concluded that HIF-1α is proven to have a crucial role in the progression and aggressiveness of AMB. Extended research regarding the crucial role of HIF-1α in the initiation of tumors and therapies aiming at HIF-1α in AMB cases might show promising outcomes in the future.

An Innovative Approach for Biocontrol of Meloidogyne incognita in Ginger Using Potential Bacteria Isolated from Indian Himalayas.

The prevalence of Meloidogyne incognita, a severe root-knot nematode, is alarmingly high in the production of ginger-a main cash crop of Himachal Pradesh, a Himalayan state of India. In order to control this through natural means, the nematicidal potential of plant growth-promoting rhizobacteria (PGPR) against M. incognita was analyzed. This is an effective alternative solution to manage nematode incidence as compared to hazardous chemicals under protected and field cultivation of ginger. In the present study an attempt has been made to isolate, characterize, and identify potential rhizobacteria associated with ginger rhizosphere and endosphere. In total, 169 bacterial isolates were isolated from ginger (Zingiber officinale) rhizosphere and endosphere of 4 different sites of Sirmaur district, screened out for multifarious PGP traits showing positive results. The combined cluster analysis and 16S rRNA genotypic analysis of selected bacterial isolates revealed that Serratia marcescens FS-23, Pseudochrobacter sp. GS-15, Stonotrophomonas pavanii HER-9, Pseudomonas brassicacearum HER-20 and Serratia marcescens IS-2 exhibited highest PGP traits. All tested bacterial isolates were capable of exerting a significant effect on mortality of juvenile M. incognita ranging upto 40-90% in laboratory experiments. Further a consortium of these screened isolates showed 86.67% reduction in gall formation by M. incognita in lab conditions. The remarkable increase to 93.24% with 138.73 q/ha with application of charcoal based bio-formulation of consortium without adding any chemical fertilizer was observed in field trials of Nohradhar of Sirmaur district. An alternative choice as a biocontrol agent as well as for PGP activities, the novel and most robust isolate Serratia marcescens IS-2 had revealed to have a variety of bioactive metabolic products with abilities against nematodes, bacteria, and fungi.

SWADESH: a multimodal multi-disease brain imaging and neuropsychological database and data analytics platform.

Multimodal neuroimaging data of various brain disorders provides valuable information to understand brain function in health and disease. Various neuroimaging-based databases have been developed that mainly consist of volumetric magnetic resonance imaging (MRI) data. We present the comprehensive web-based neuroimaging platform "SWADESH" for hosting multi-disease, multimodal neuroimaging, and neuropsychological data along with analytical pipelines. This novel initiative includes neurochemical and magnetic susceptibility data for healthy and diseased conditions, acquired using MR spectroscopy (MRS) and quantitative susceptibility mapping (QSM) respectively. The SWADESH architecture also provides a neuroimaging database which includes MRI, MRS, functional MRI (fMRI), diffusion weighted imaging (DWI), QSM, neuropsychological data and associated data analysis pipelines. Our final objective is to provide a master database of major brain disease states (neurodegenerative, neuropsychiatric, neurodevelopmental, and others) and to identify characteristic features and biomarkers associated with such disorders.

Coagulopathy in the absence of overt DIC in postoperative neurosurgical patients is a strong predictor of poor outcome.

OBJECTIVES: To assess the prevalence of coagulopathy in postoperative neurosurgical patients and correlate it with the outcome. MATERIALS AND METHOD: This longitudinal study was conducted in a tertiary care hospital in the Department of Pathology and Neurosurgery. Ethical approval was taken from the Institutional Ethical Committee - Human Research. Seventy-two (72) participants were recruited within 48 hours of surgery after obtaining consent. Complete clinical and surgical details were recorded. A 6.5 mL venous sample was collected and dispensed in two separate vials. The EDTA sample was run within 2 hours of collection on an automated hematology analyzer to obtain complete blood counts, including platelet count. The citrated sample was run on a fully automated coagulometer to determine PT, APTT, plasma fibrinogen, FVIII assay, and D-dimer levels. Subjects with a DIC-ISTH score of 5 or more were excluded. Coagulopathy was defined as three or more coagulation parameters deranged in a patient. All patients were followed up for the outcome. The outcome was correlated with coagulopathy, and a p-value less than 0.05 was considered statistically significant. RESULTS: The study found that the number of hemostatic parameters deranged correlated with outcome (P < 0.001). The proportion of patients with coagulopathy was 32/72 (44.4%), while those without coagulopathy were 40/72 (55.6%). Of patients with coagulopathy, 87.5% (28/32) had an adverse outcome, while 12.5% (4/32) had a favorable outcome. The difference was found to be statistically significant (P < 0.001). CONCLUSIONS: Coagulopathy, defined as the derangement of three or more parameters, is a predictor of poor outcomes in postoperative neurosurgical patients. This timely recognition of coagulopathy can help triage patients requiring appropriate blood products, significantly reducing morbidity and mortality associated with postoperative neurosurgical patients.

Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.

Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success with current therapies. In addition, the high cost of new anti-cancer drugs creates barriers in meeting the medical needs of cancer patients, especially in developing countries. The lengthy and costly process of developing novel drugs further hinders drug discovery and clinical implementation. Therefore, there has been a growing interest in repurposing approved drugs for other diseases to address the urgent need for effective cancer treatments. The aim of this comprehensive review is to provide an overview of the potential of approved non-oncology drugs as therapeutic options for cancer treatment. These drugs come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, and antifungals, and have demonstrated significant antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties. A systematic review of the literature was conducted to identify relevant studies on the repurposing of approved non-oncology drugs for cancer therapy. Various electronic databases, such as PubMed, Scopus, and Google Scholar, were searched using appropriate keywords. Studies focusing on the therapeutic potential, mechanisms of action, efficacy, and clinical prospects of repurposed drugs in cancer treatment were included in the analysis. The review highlights the promising outcomes of repurposing approved non-oncology drugs for cancer therapy. Drugs belonging to different therapeutic classes have demonstrated notable antitumor effects, including inhibiting cell proliferation, promoting apoptosis, modulating the immune response, and suppressing metastasis. These findings suggest the potential of these repurposed drugs as effective therapeutic approaches in cancer treatment. Repurposing approved non-oncology drugs provides a promising strategy for addressing the urgent need for effective and accessible cancer treatments. The diverse classes of repurposed drugs, with their demonstrated antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties, offer new avenues for cancer therapy. Further research and clinical trials are warranted to explore the full potential of these repurposed drugs and optimize their use in treating various cancer types. Repurposing approved drugs can significantly expedite the process of identifying effective treatments and improve patient outcomes in a cost-effective manner.