Non-coding RNA's prevalence as biomarkers for prognostic, diagnostic, and clinical utility in breast cancer.

Noncoding RNAs (ncRNAs), which make up a significant portion of the mammalian transcriptome and plays crucial regulatory roles in expression of genes and other biological processes, have recently been found. The most extensively researched of the sncRNAs, microRNAs (miRNAs), have been characterized in terms of their synthesis, roles, and significance in the tumor development. Its crucial function in the stem cell regulation, another class of sncRNAs known as aspirRNAs, has attracted attention in cancer research. The investigations have shown that long non-coding RNAs have a crucial role in controlling developmental stages, such as mammary gland development. Additionally, it has been discovered that lncRNA dysregulation precedes the development of several malignancies, including breast cancer. The functions of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the onset and development of the breast cancer are described in this study. Additionally, future perspectives of various ncRNA-based diagnostic, prognostic, and therapeutic approaches also discussed.

Repurposing Drugs to Modulate Sortilin: Structure-Guided Strategies Against Atherogenesis, Coronary Artery Disease, and Neurological Disorders.

Sortilin (SORT1) is a multifunctional protein intricately involved in atherogenesis, coronary artery disease (CAD), and various neurological disorders. It has materialized as a potential pharmacological target for therapeutic development due to its diverse biological roles in pathological processes. Despite its central role under these conditions, effective therapeutic strategies targeting SORT1 remain challenging. In this study, we introduce a drug repurposing strategy guided by structural insights to identify potent SORT1 inhibitors with broad therapeutic potential. Our approach combines molecular docking, virtual screening, and molecular dynamics (MD) simulations, enabling the systematic evaluation of 3648 FDA-approved drugs for their potential to modulate SORT1. The investigation reveals a subset of repurposed drugs exhibiting highly favorable binding profiles and stable interactions within the binding site of SORT1. Notably, two hits, ergotamine and digitoxin, were carefully chosen based on their drug profiles and subjected to analyze their interactions with SORT1 and stability assessment via all-atom MD simulations spanning 300 ns (ns). The structural analyses uncover the complex binding interactions between these identified compounds and SORT1, offering essential mechanistic insights. Additionally, we explore the clinical implications of repurposing these compounds as potential therapeutic agents, emphasizing their significance in addressing atherogenesis, CAD, and neurological disorders. Overall, this study highlights the efficacy of structure-guided drug repurposing and provides a solid foundation for future research endeavors aimed at the development of effective therapies targeting SORT1 under diverse pathological conditions.

Exogenous salicylic acid mediated herbicide (Paraquat) resistance in cyanobacterial biofertilizer Microchaete sp. NCCU-342.

Paddy field farming remains the dominant form of growing rice in modern times as the rice is the staple food for over half the world's population and is closely associated with food security and political stability of many countries. Record increase in rice production have been observed since the start of the Green Revolution. India is one of the largest paddy producer and exporter in the world. However, constant use of chemical herbicide like paraquat had shown adverse impact on the rice yield. Non-target organisms of the habitat including cyanobacterial paddy biofertilizer face the herbicide toxicity and are unable to perform efficiently their role as biofertilizer. Therefore, in the present study, an attempt has been made to enhance the paraquat resistance in rice biofertilizer (Microchaete sp. NCCU-342) by exogenous addition of salicylic acid. Paraquat showed toxicity in Microchaete sp. NCCU-342 in a dose-dependent manner. Concentration of paraquat >1.0 µM exhibited lethal effect since the beginning. Through successive narrow range experiment, LD50 value of paraquat was obtained as 0.6 µM. Biomass exposed to paraquat (LD50 value) and salicylic acid (0.3 mM) showed mitigation in free radical production (2.20 % MDA and 1.69 % H2O2) and enhancement in the activity of the antioxidant enzymes activity, i.e. SOD, CAT, APX (137.76 %, 87.45 %, 118 %, respectively) and osmolytes (3.8 % proline and 21.51% sucrose). Thus, for sustainable agricultural practice, especially for paddy field cyanobacterial biofertilizer, application of salicylic acid or organism with higher salicylic acid production ability may be an alternative to overcome the paraquat toxicity.

Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods.

Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Protein-protein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of LAMA2, TIMP4, and TMTC1 on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, LAMA2, TMTC1, ADAMTS5, TIMP4, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that LAMA2, TMTC1, and TIMP4 were significantly expressed among different age groups of patients. LAMA2 and TIMP4 were found significantly associated and TMTC1 was found less correlated with breast cancer occurrence. We found that the expression level of LAMA2, TIMP4, and TMTC1 was abnormal in all TCGA tumors and significantly associated with poor survival.

Media engineering in marine diatom Phaeodactylum tricornutum employing cost-effective substrates for sustainable production of high-value renewables.

Phaeodactylum tricornutum is a marine diatom, rich in omega-3 polyunsaturated fatty acids especially eicosapentaenoic acid (EPA) and brown pigment, that is, fucoxanthin. These high-value renewables (HVRs) have a high commercial and nutritional relevance. In this study, our focus was to enhance the productivities of such renewables by employing media engineering strategy via., photoautotrophic (P1, P2, P3) and mixotrophic (M1, M2, M3, M4) modes of cultivation with varying substrate combinations of carbon (glycerol: 0.1 m) and nitrogen (urea: 441 mm and/or sodium nitrate: 882 mm). Our results demonstrate that mixotrophic [M4] condition supplemented with glycerol (0.1 m) and urea (441 mm) feed enhanced productivities (mg L-1  day-1 ) as follows: biomass (770.0), total proteins (36.0), total lipids (22.0), total carbohydrates (23.0) with fatty acid methyl esters (9.6), EPA (2.7), and fucoxanthin (1.1), respectively. The overall yield of EPA represents 28% of total fatty acids in the mixotrophic [M4] condition. In conclusion, our improved strategy of feeding urea to a glycerol-supplemented medium defines a new efficient biomass valorization paradigm with cost-effective substrates for the production of HVRs in oleaginous diatoms P. tricornutum.

Screening, characterisation and bioactivities of green fabricated TiO2 NP via cyanobacterial extract.

The present study was aimed at exploring 37 strains of cyanobacteria for the biofabrication of TiO2 NP and evaluation of their antioxidant, antifungal, antibacterial and hemolytic activity. Screening of cyanobacterial strains was done via SEM, followed by optimisation and characterisation of the best strain. Synechocystis NCCU-370 appeared as the best strain for the synthesis of TiO2 NP in terms of size (73.39 nm) and time (24 h) after screening. Following optimisation, nanoparticles were synthesised in 12 h having an average grain size of 16 nm. The aqueous extract preparation required heating of 5 mg/ml of powdered biomass to 60 °C for 10 min. Optimum conditions for the synthesis of TiO2 NP were found to be pH 7, 30 °C and 12-h cell extract exposure to 0.1 mM of salt. Antioxidant activity was evaluated via DPPH, ABTS and FRAP assay. Antifungal potential was explored against Candida albicans (MIC = 125 µg/ml), Candida glabrata (MIC = 500 µg/ml) and Candida tropicalis (MIC = 250 µg/ml), whereas antibacterial potential was gauged for Bacillus cereus (MIC = 31.25 µg/ml), Escherichia coli (MIC = 31.25 µg/ml) and Klebsiella pneumoniae (MIC = 500 µg/ml) strains. Biogenic TiO2 NP demonstrated partial synergistic effect and excellent biocompatibility.

Mitigative effect of biosynthesized SeNPs on cyanobacteria under paraquat toxicity.

Increasing population has resulted in increased food demand. Pesticides like paraquat (PQ) have been used indiscriminately to increase the growth and yield of crops. However, this has adversely affected a wide spectrum of non-target organisms like cyanobacteria that are used as a bio-fertilizer in the rice field. In the present study, biogenic- Gloeocaspa gelatinosa NCCU -430 mediated selenium nanoparticles (SeNPs) were synthesized and characterized using different techniques including UV-Visible spectroscopy, XRD, FTIR, TEM and SEM-EDX for their use as PQ toxicity mitigator in cyanobacterial biofertilizer (Anabaena variabilis NCCU-442). Therefore, a comparative study was performed among control, PQ, SeNPs and SeNPs+PQ to check the efficacy of SeNPs in mitigation of PQ induced toxicity. Supplementation of SeNPs in PQ treated culture enhanced antioxidant enzymes activity i.e., SOD (7.55%), CAT (57.94%), APX (17.45%) and GR (14.72%) as compared to only PQ treated culture. The outcomes of the present study suggested that SeNPs can ameliorate the PQ induced stress that may be used in sustainable rice cultivation needed for filing the gap between requirement and supply.

Circadian clock modulating small molecules repurposing as inhibitors of SARS-CoV-2 Mpro for pharmacological interventions in COVID-19 pandemic.

The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency warranting the development of targeted treatment. The main protease Mpro is considered as a key drug target in coronavirus infections because of its vital role in the proteolytic processing of two essential polyproteins required for the replication and transcription of viral RNA. Targeting and inhibiting the Mpro activity represents a valid approach to prevent the SARS-CoV-2 replication and spread. Based on the structure-assisted drug designing, here we report a circadian clock-modulating small molecule "SRT2183" as a potent inhibitor of Mpro to block the replication of SARS-CoV-2. The findings are expected to pave the way for the development of therapeutics for COVID-19.

Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.

OBJECTIVE: To determine mutations in the SRY gene in two sisters with 46, XY karyotype. DESIGN: Case report. SETTING: Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia. PATIENT(S): Two sisters aged 23 and 27 years old with primary amenorrhea. INTERVENTION(S): Endocrine, mutations in the SRY gene, and DNA binding ability. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels, DNA sequence findings. RESULT(S): We found a new point mutation in the SRY gene in patient 1 at position +275 (A>T), which results in amino acid change (K92M). In patient 2, we found a double mutation in the SRY gene at two different loci. The first mutation is a substitution of C at +352, resulting in a change of amino acid (A118P), and second is deletion of T, resulting in a frame shift within a highly conserved DNA-binding motif-high mobility group box at +379 (T127IfsX179). Electrophoretic mobility shift assay showed that mutant K92M and A118P show reduced and greatly reduced binding ability, respectively. These mutations have the potential to interfere with protein-DNA binding activity and nuclear localization necessary for interactions of these proteins with DNA. CONCLUSION(S): Our results suggest involvement of the SRY gene in sex reversal, which supports the relationship between SRY alterations, gonadal dysgenesis, and/or primary infertility, and provides further evidence of a high-mobility group box significance in DNA-binding/-bending properties.