In-silico screening of bioactive compounds of Moringa oleifera as potential inhibitors targeting HIF-1α/VEGF/GLUT-1 pathway against Breast Cancer.

OBJECTIVES: Breast cancer is among the most heterogeneous and aggressive diseases and a foremost cause of death in women globally. Hypoxic activation of HIF-1α in breast cancers triggers the transcription of a battery of genes encoding proteins that facilitate tumor growth and metastasis and is correlated with a poor prognosis. Based on the reported cytotoxic and anti-cancer properties of Moringa oleifera (Mo), this study explores the inhibitory effect of bioactive compounds from M. oleifera and breast cancer target proteins HIF-1α, VEGF, and GLUT-1 in silico. METHODS: The X-ray crystallographic structures of HIF-1α, VEGF, and GLUT1 were sourced from the Protein Data Bank (PDB) and docked with 70 3D PubChem structures of bioactive compounds of M. oleifera using AutoDock Vina, and binding modes were analyzed using Discovery Studio. Five compounds with the highest binding energies were selected and further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. RESULTS: Out of the screened 70 bioactive compounds, the top five compounds with the best binding energies were identified namely Apigenin, Ellagic Acid, Isorhamnetin, Luteolin, and Myricetin with each receptor. Molecular docking results indicated that the ligands interact strongly with the target HIF-1α, VEGF, and GLUT-1 receptors through hydrogen bonds and hydrophobic interactions. These compounds showed favorable drug-like and pharmacokinetic properties, possessed no substantial toxicity, and were fairly bioavailable. CONCLUSIONS: Results suggested that the compounds possess strong potential in developing putative lead compounds targeting HIF-1α that are safe natural plant-based drugs against breast cancer.

Targeted chemo-phototherapy in red light with novel doxorubicin and iron(III) complex-functionalized gold nanoconjugate (Dox-Fe@FA-AuNPs).

The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects, despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5 ± 16.52 µg mL-1; MDA-MB-231: 112.0 ± 12.31 µg mL-1; MDA-MB-231 (3D): 156.31 ± 19.35 µg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.

Exploring New COVID-19 Incertitude: JN.1 Variant- JN.1: The Queer Bird Among Omicron Sublineages.

COVID-19 pandemic is casting a long shadow, and the appearance of the JN.1 variety calls attention to the necessity of maintaining heightened awareness. It considers the strength that has been developed via immunization programs and the necessity of global collaboration to find a solution in light of the emergence of new strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Phylogenetically, the SARS-CoV-2 Omicron XBB lineages, which include EG.5.1 and HK.3, are different from the SARS-CoV-2 BA.2.86 lineage, which was initially discovered in August 2023. More than 30 mutations in the spike (S) protein are carried by BA.2.86 compared to XBB and BA.2, suggesting a high potential for immune evasion. JN.1 (BA.2.86.1.1), a descendant of BA.2.86, appeared in late 2023 after the format had undergone evolution. JN.1 carries three mutations in proteins that do not include S, as well as S:L455S. As previously demonstrated, the HK.3 and other "FLip" variations possess the S:L455F mutation, which enhances transmissibility and immune escape capacity in comparison to the parental EG.5.1 variety. This mutation is a characteristic of JN.1. The COVID-19 virus is dynamic and evolves over time. New varieties can sometimes spread more quickly or effectively after these alterations. If that happens, the new variant has a chance to outpace the current varieties in terms of frequency.

Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.

Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive ß subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.

Molecular perspectives on systemic priming and concomitant immunity in colorectal carcinoma.

The progression of metastasis, a complex systemic disease, is facilitated by interactions between tumor cells and their isolated microenvironments. Over the past few decades, researchers have investigated the metastatic spread of cancer extensively, identifying multiple stages in the process, such as intravasation, extravasation, tumor latency, and the development of micrometastasis and macrometastasis. The premetastatic niche is established in target organs by the accumulation of aberrant immune cells and extracellular matrix proteins. The "seed and soil" idea, which has become widely known and accepted, is being used to this day to guide cancer studies. Changes in the local and systemic immune systems have a major impact on whether an infection spreads or not. The belief that the immune response may play a role in slowing tumor growth and may be beneficial against the metastatic disease underpins the responsiveness shown in the immunological landscape of metastasis. Various hypotheses on the phylogenesis of metastases have been proposed in the past. The primary tumor's secreting factors shape the intratumoral microenvironment and the immune landscape, allowing this progress to be made. Therefore, it is evident that among disseminated tumor cells, there are distinct phenotypes that either carry budding for metastasis or have the ability to obtain this potential or in systemic priming through contact with substantial metastatic niches that have implications for medicinal chemistry. Concurrent immunity signals that the main tumor induces an immune response that may not be strong enough to eradicate the tumor. Immunotherapy's success with some cancer patients shows that it is possible to effectively destroy even advanced-stage tumors by modifying the microenvironment and tumor-immune cell interactions. This review focuses on the metastasome in colorectal carcinoma and the therapeutic implications of site-specific metastasis, systemic priming, tumor spread, and the relationship between the immune system and metastasis.

Breast cancer stem cells as novel biomarkers.

Breast cancer is the most common cancer and the leading cause of mortality worldwide. Despite advancements in detection and treatment, it remains a major cause of cancer-related deaths in women. Breast cancer stem cells (BCSCs) are a crucial group of cells responsible for carcinogenesis, metastasis, medication resistance, and tumor recurrence. Identifying and understanding their molecular pathways is essential for developing effective breast cancer therapy. BCSCs are responsible for tumor genesis, development, metastasis, treatment resistance, and recurrence. Biomarkers are essential tools for identifying high-risk patients, improving diagnostic accuracy, developing follow-up programs, assessing treatment susceptibility, and predicting prognostic outcomes. Stem cell intervention therapy can provide specialized tools for precision therapy. Biomarker analysis in cancer patients is crucial to identify cells associated with disease progression and post-therapeutic relapse. However, negative post-therapeutic impacts can enhance cancer stemness by boosting BCSCs plasticity phenotypes, activating stemness pathways in non-BCSCs, and promoting senescence escape, leading to tumor relapse and metastasis. Despite the advancements in precision medicine, challenges persist in identifying stem cell markers, limiting the number of eligible patients for treatment. The diversity of biomedical research hinders the development of individualization-based preventative, monitoring, and treatment strategies, especially in oncology. Integrating and interpreting clinical and scientific data remains challenging. The development of stem cell-related indicators could significantly improve disease precision, enabling stem cell-targeted therapy and personalized treatment plans, although BCSCs are promising for breast cancer treatment optimization, serving as biomarkers for current therapy modalities. This summary discusses recent advancements in breast cancer stem cell research, including biomarkers, identification methods, molecular mechanisms, and tools for studying their biological origin and lineage development for precision medicine.

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21.

BACKGROUND: Prior evidence demonstrated that Regulator of G protein Signaling 6 (RGS6) translocates to the nucleolus in response to cytotoxic stress though the functional significance of this phenomenon remains unknown. METHODS: Utilizing in vivo gene manipulations in mice, primary murine cardiac cells, human cell lines and human patient samples we dissect the participation of a RGS6-nucleolin complex in chemotherapy-dependent cardiotoxicity. RESULTS: Here we demonstrate that RGS6 binds to a key nucleolar protein, Nucleolin, and controls its expression and activity in cardiomyocytes. In the human myocyte AC-16 cell line, induced pluripotent stem cell derived cardiomyocytes, primary murine cardiomyocytes, and the intact murine myocardium tuning RGS6 levels via overexpression or knockdown resulted in diametrically opposed impacts on Nucleolin mRNA, protein, and phosphorylation.RGS6 depletion provided marked protection against nucleolar stress-mediated cell death in vitro, and, conversely, RGS6 overexpression suppressed ribosomal RNA production, a key output of the nucleolus, and triggered death of myocytes. Importantly, overexpression of either Nucleolin or Nucleolin effector miRNA-21 counteracted the pro-apoptotic effects of RGS6. In both human and murine heart tissue, exposure to the genotoxic stressor doxorubicin was associated with an increase in the ratio of RGS6/Nucleolin. Preventing RGS6 induction via introduction of RGS6-directed shRNA via intracardiac injection proved cardioprotective in mice and was accompanied by restored Nucleolin/miRNA-21 expression, decreased nucleolar stress, and decreased expression of pro-apoptotic, hypertrophy, and oxidative stress markers in heart. CONCLUSION: Together, these data implicate RGS6 as a driver of nucleolar stress-dependent cell death in cardiomyocytes via its ability to modulate Nucleolin. This work represents the first demonstration of a functional role for an RGS protein in the nucleolus and identifies the RGS6/Nucleolin interaction as a possible new therapeutic target in the prevention of cardiotoxicity.

Hyperoxic-hypoxic Paradox: Breast Cancer Microenvironment and an Innovative Treatment Strategy.

A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells. Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.

Role of Protein Ubiquitination and HIF Signaling in the Evolution of Hypoxic Breast Cancer.

Alternations in protein ubiquitination along with hypoxia-inducible factor (HIF) signaling contribute to tumorigenesis and breast tumor advancement. Ubiquitination is an impulsive process, which is coordinately governed by E3 ligases and deubiquitinases (DUBs), that have come out as charismatic therapeutic targets. HIF expression, as well as the transcriptional process in malignancies, are frequently elevated, resulting in pitiable clinical outcomes. According to increasing research, multiple E3 ligases, in addition to UBDs work together to modulate HIF expression and activity, permitting breast cancer cells to make out a hypoxic milieu. On the other hand, hypoxia and HIF signaling regulate numerous E3 ligases as well as DUBs. Interpreting involved networks connecting E3 ligase, DUBS, and HIF will reveal profound mechanisms of physiological response to hypoxia and aid in the discovery of new molecular references for cancer management. The present state of knowledge about the entire kinship among E3 ligase, DUBs, and HIF signaling is reviewed here, emphasizing using E3 ligase or DUB inhibitors in breast cancer.

Folate-assisted targeted photocytotoxicity of red-light-activable iron(III) complex co-functionalized gold nanoconjugates (Fe@FA-AuNPs) against HeLa and triple-negative MDA-MB-231 cancer cells.

Photo-redox chemistry resulting from ligand to metal charge transfer in red-light-activable iron(III) complexes could be a potent strategic tool for next-generation photochemotherapeutic applications. Herein, we developed an iron(III) complex and folate co-functionalized gold nanoconjugate (Fe@FA-AuNPs) and thoroughly characterized it with NMR, ESI MS, UV-visible, EPR, EDX, XPS, powder X-ray diffraction, TEM and DLS studies. There was a remarkable shift in the SPR band of AuNPs to 680 nm, and singlet oxygen (1O2) and hydroxyl radicals were potently generated upon red-light activation, which were probed by UV-visible and EPR spectroscopic assays. Cellular uptake studies of the nanoconjugate (Fe@FA-AuNPs) revealed significantly higher uptake in folate(+) cancer cells (HeLa and MDA-MB-231) than folate(-) (A549) cancer cells or normal cells (HPL1D), indicating the targeting potential of the nanoconjugate. Confocal imaging indicated primarily mitochondrial localization. The IC50 values of the nanoconjugate determined from a cell viability assay in HeLa, MDA-MB-231, and A549 cells were 27.83, 39.91, and 69.54 µg mL-1, respectively in red light, while in the dark the values were >200 µg mL-1; the photocytotoxicity was correlated with the cellular uptake of the nanoconjugate. The nanocomposite exhibited similar photocytotoxicity (IC50 in red light, 37.35 ± 8.29 µg mL-1 and IC50 in the dark, >200 µg mL-1). Mechanistic studies revealed that intracellular generation of ROS upon red-light activation led to apoptosis in HeLa cells. Scratch-wound-healing assays indicated the inhibition of the migration of MDA-MB-231 cells treated with the nanoconjugate and upon photo-activation. Overall, the nanoconjugate has emerged as a potent tool for next-generation photo-chemotherapeutics in the clinical arena of targeted cancer therapy.

A New-fangled COVID-19 Variant, Eris, Might be the One to Lookout in 2023 or far from Over.

Coronavirus Disease-19 (COVID-19) is an infectious disease brought on by the extremely pathogenic and contagious severe acute respiratory syndrome-virus-2 (SARS-CoV-2). The agenda for the COVID-19 pandemic is dynamic and includes recent developments. Seven variants under monitoring (VUMs), one variant of interest (VOI), XBB.1.5, and their offspring lineages are currently being actively monitored by WHO. The VUMs are BA.2.75, CH.1.1, BQ.1, XBB (with the exception of XBB.1.5, XBB.1.16, and XBB.1.9.1), XBF, and XBB.1.16. With 95 countries having reported finding XBB.1.5 (VOI), it is still the most common strain worldwide, responsible for 47.9% of cases from epidemiological January to March 2023. Seventy nations discovered XBB.1.5 in February and March 2023 and posted sequencing data to GISAID. Of the 43 nations that uploaded more than 50 sequences, XBB.1.5 prevalence has increased to more than 50% in 11 nations. Over 23000 deaths and 3 million new cases were recorded globally in March and April 2023. Worldwide detection of a new COVID-19 strain has prompted specialists to issue a warning that the virus is "circulating unchecked". The Greek goddess of conflict and discord Eris has inspired the nicknaming of EG 5.1, a subvariant of Omicron. The strain is becoming more prevalent in the USA and cases are increasing in the UK. The severity of each SARS-CoV- 2 variant has been comparable, although a more severe form might develop. Eris is an ancestor of Omicron and exhibits some of its characteristics. Reinfection risk can be influenced by a variety of variables, including age, location, and health equity and the COVID-19 vaccine is more or less effective depending on the strain.

Innovation and Patenting Activities During COVID-19 and Advancement of Biochemical and Molecular Diagnosis in the Post- COVID-19 Era.

The COVID-19 pandemic is to escalate globally and acquire new mutations quickly, so accurate diagnostic technologies play a vital role in controlling and understanding the epidemiology of the disease. A plethora of technologies acquires diagnosis of individuals and informs clinical management of COVID. Some important biochemical parameters for COVID diagnosis are the elevation of liver enzymes, creatinine, and nonspecific inflammatory markers such as C-reactive protein (CRP) and Interleukin 6 (IL-6). The main progression predictors are lymphopenia, elevated D-dimer, and hyperferritinemia, although it is also necessary to consider LDH, CPK, and troponin in the marker panel of diagnosis. Owing to the greater sensitivity and accuracy, molecular technologies such as conventional polymerase chain reaction (PCR), reverse transcription (RT)-PCR, nested PCR, loop-mediated isothermal amplification (LAMP), and xMAP technology have been extensively used for COVID diagnosis for some time now. To make so many diagnostics accessible to general people, many techniques may be exploited, including point of care (POC), also called bedside testing, which is developing as a portable promising tool in pathogen identification. Some other lateral flow assay (LFA)-centered techniques like SHERLOCK, CRISPR-Cas12a (AIOD-CRISPR), and FNCAS9 editor limited uniform detection assay (FELUDA), etc. have shown auspicious results in the rapid detection of pathogens. More recently, low-cost sequencing and advancements in big data management have resulted in a slow but steady rise of next-generation sequencing (NGS)-based approaches for diagnosis that have potential relevance for clinical purposes and may pave the way toward a better future. Due to the COVID-19 pandemic, various institutions provided free, specialized websites and tools to promote research and access to critically needed advanced solutions by alleviating research and analysis of data within a substantial body of scientific and patent literature regarding biochemical and molecular diagnosis published since January 2020. This circumstance is unquestionably unique and difficult for anyone using patent information to find pertinent disclosures at a specific date in a trustworthy manner.

Oxidative versus Reductive Stress in Breast Cancer Development and Cellular Mechanism of Alleviation: A Current Perspective with Anti-breast Cancer Drug Resistance.

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.

Innovative Nanomaterials for Targeting Hypoxia to Improve Treatment for Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a high rate of metastases, a short overall survival time, and a poor response to targeted therapy. Improving tumor hypoxia by lowering the oxygen consumption rate of breast tumor cells is a powerful strategy. A viable way to address this issue is to improve therapeutic efficacy by improving the effectiveness of radiation and overcoming drug resistance in TNBC treatment by controlling hypoxia in the tumor microenvironment. The failure of radiation and chemotherapy in TNBC is frequently caused by hypoxia. In TNBC therapy, novel nanomaterials are used for oxygen delivery or generation to affect the tumor microenvironment to improve the effects of ionizing radiation using nanoplatforms. One of the growing fields is novel nano-based drug delivery devices for hypoxic regions and hypoxia- inducible factor-1 (HIF1) targeted therapeutics. Biocompatible nanoparticles may be used in the treatment of TNBC patients in the clinic. Because of the rising market and competition, intellectual property rights (IPR), patents, and tactics may be critically considered. To better comprehend the current state of IPR and patents in cancer nanotechnology, this overview examines recent advances and sophisticated protection measures in this area.

Multi-level Analysis of HbA1c in Diagnosis and Prognosis of Diabetic Patients.

BACKGROUND: Type 2 diabetes (T2D), a multifaceted metabolic disorder, may cause health tribulations and changes in biochemical blood markers. Other research has examined the relationships between several biomarkers and the risk of T2D. Few studies have examined the relationships between these biomarkers and potential changes to the network of biomarkers associated with diabetes. METHOD: Glycated hemoglobin, or HbA1C, is used to evaluate and track the blood glucose history throughout the previous two to three months of testing. The ability to reflect the cumulative glycemic history of the previous two to three months makes HbA1c an essential biomarker of long-term glycemic control. HbA1c offers a trustworthy indicator of chronic hyperglycemia and strongly correlates with the likelihood of long-term consequences from diabetes. RESULT: Additionally, elevated HbA1c has been recognized as a stand-alone risk factor for patients with and without diabetes developing coronary heart disease and stroke. One HbA1c test offers a wealth of information that makes it a reliable biomarker for the diagnosis and prognosis of diabetes. A clinical examination may be required to establish the connection between diabetes, prediabetes, biochemical blood indicators, age, and body mass index (BMI). CONCLUSION: We observed that diabetes, BMI, age, HbA1c, cholesterol, triglycerides, LDL, VLDL, and HDL were all linked using multivariate analysis.

Clinical Risk Assessment and Comparison of Bias Between Laboratory Methods for Estimation of HbA1c for Glycated Hemoglobin in Hyperglycemic Patients.

INTRODUCTION: Hemoglobin A1c (HbA1c), also known as glycated hemoglobin, is a blood test used to evaluate and track a patient's blood sugar levels over the previous 2-3 months. We have compared the analytical performance of the D10 hemoglobin (HPLC) testing system to that of the immunoturbidimetric technique, which is a light-scattering immunoassay. OBJECTIVES: To assess the clinical risk assessment between two methods (Compare the two Immunoturbidometric methods (AU680) vs HPLC method (D10)) in hyperglycemic patients and assess the acceptability of the respective methods in the clinical biochemistry Laboratory. METHODS: The charge of the globins in Hb was used as the basis for the HPLC method used to measure HbA1c. HPLC detects and quantifies even the tiniest Hb fractions and the full spectrum of Hb variants. HbA1c was measured using the immunoturbidimetric (AU 680 Beckmann coulter analyzer) and high-performance liquid chromatography (HPLC) techniques. Experiments also made use of immunoturbidimetric techniques (using an AU 680 Beckmann coulter analyzer equipment). RESULTS: There is no statistically significant difference in HbA1c readings between male and female patients, as measured by either the Immunoturbidimetric or HPLC techniques. CONCLUSION: The immunoturbidimetric and high-performance liquid chromatography techniques for estimating HbA1c yielded identical results. From the results of this study, we may deduce that both techniques are valid for estimating HbA1c. As a result, it may be suggested that both approaches can be used to estimate HbA1c in diabetic individuals.

Memory Reflections of the Microbiota-Gut and Oligodendrocyte Axis.

Memory is the persisting consequence of cognitive activities instigated by and engrossed on exterior information from the environment and commenced by an intensive on internal mental representations. Establishing a gut-brain axis (GBA) in health and disease has recently brought the gut, the main portal of communication with the external environment, to the forefront of this interaction. Dietary stimuli have long been linked to brain development, behavioral responses, and memory reflections. Vagus nerve, immune system, bacterial metabolites and products are just a few of the linkages that make up the GBA, a bidirectional arrangement of signaling pathways that connects the neurological system with the gastrointestinal tract. GBA involves two-way communication between central and enteric neural systems, connecting the brain's affective and cognitive regions to peripheral activities of the intestine. Recent scientific progress has highlighted the significance of gut microbiota in affecting these relationships. By controlling myelination at the prefrontal cortex, a crucial area for multifaceted cognitive behavior forecast and decision-making, this axis influences social behavior, including memory reflections. Humans may experience late myelination of the prefrontal cortex's axonal projections into the third decade of life, making it vulnerable to outside factors like microbial metabolites. It has been demonstrated that changes in the gut microbiome can change the microbial metabolome's composition, impacting highly permeable bioactive chemicals like p-cresol that may hinder oligodendrocyte differentiation. This review will discuss the memory reflections of the microbiota-gut and oligodendrocyte axis. Adopting this concept should encourage a new arena of thinking that recognizes the intricate central and periphery dynamics influencing behavior and uses that knowledge to develop novel therapies and interventions for maladjusted memory and learning systems.

Emerging Role of Ferroptosis in Breast Cancer: Characteristics, Therapy, and Translational Implications for the Present and Future.

Ferroptosis is a nonapoptotic, iron-dependent form of cell death that can be actuated in disease cells by expected improvements and manufactured specialists. Different studies have recently resurrected the role of this newly discovered cell death pathway and demonstrated its efficacy in treating breast cancer. Breast cancer is the most well-known type of cancer among women worldwide. Despite many years of research focusing on cell death in breast cancer, counting apoptosis, clinical treatment leftovers are difficult due to the high likelihood of recurrence. Ferroptosis is defined by a lack of lipid peroxide repair capacity by phospholipid hydroperoxides GPX4, accessibility of redox-active iron, and followed oxidation of polyunsaturated fatty acids acid-containing phospholipids signalling, amino acid and iron metabolism, ferritinophagy, epithelial-to-mesenchymal transition, cell adhesion, and mevalonate and phospholipid biosynthesis can all be factors that influence ferroptosis susceptibility. Ferroptosis, an iron-dependent controlled cell death caused by excessive lipid peroxidation, has been entwined in breast cancer development and therapeutic response for the past decade. Advances in enhancing clinical drugs targeting ferroptosis are developing silver linings to treat breast cancer. Ferroptosis is influenced by metabolism and the expression of certain genes, making it a prospective therapeutic target for monitoring malignant growth and an appealing target for precision cancer medication disclosure. In the coming years, research into biomarkers to follow ferroptosis in patients with breast cancer and the course of events and the subsequent use of novel ferroptosis-based treatments will be captious. We present a fundamental analysis of the actual understanding of molecular mechanisms along with regulatory networks associated with ferroptosis, expected physiological functions in growth concealment, ferroptosis-associated differentially expressed genes, treatment targeting potential, and recent advances in the development of therapeutic strategies in this review.

Potential anti-cancer activity of Moringa oleifera derived bio-active compounds targeting hypoxia-inducible factor-1 alpha in breast cancer.

Breast cancer (BC) will become a highly detected malignancy in females worldwide in 2023, with over 2 million new cases. Studies have established the role of hypoxia-inducible factor-1α (HIF1α), a transcription factor that controls cellular response to hypoxic stress, and is essential for BC spread. HIF-1 is implicated in nearly every critical stage of the metastatic progression, including invasion, EMT, intravasation, extravasation, angiogenesis, and the formation of metastatic niches. HIF-1 overexpression has been associated with poor prognosis and increased mortality in BC patients. This is accomplished by controlling the expression of HIF-1 target genes involved in cell survival, angiogenesis, metabolism, and treatment resistance. Studies have indicated that inhibiting HIF-1 has an anti-cancer effect on its own and that inhibiting HIF-1-mediated signaling improves the efficacy of anti-cancer therapy. Approximately 74 % of recognized anti-cancer drugs are sourced from plant species. Studies on anti-cancer characteristics of phytochemicals derived from Moringa oleifera (MO), also known as the 'Tree of Life', have revealed a high therapeutic potential for BC. In this review, we have highlighted the various mechanisms through which bioactive compounds present in MO may modulate HIF and its regulatory genes/pathways, to prove their efficacy in treating and preventing BC.

Cardiac RGS7 and RGS11 drive TGFß1-dependent liver damage following chemotherapy exposure.

Off target damage to vital organ systems is an unfortunate side effect of cancer chemotherapy and remains a major limitation to the use of these essential drugs in the clinic. Despite decades of research, the mechanisms conferring susceptibility to chemotherapy driven cardiotoxicity and hepatotoxicity remain unclear. In the livers of patients with a history of chemotherapy, we observed a twofold increase in expression of G protein regulator RGS7 and a corresponding decrease in fellow R7 family member RGS11. Knockdown of RGS7 via introduction of RGS7 shRNA via tail vein injection decreased doxorubicin-induced hepatic collagen and lipid deposition, glycogen accumulation, and elevations in ALT, AST, and triglycerides by approximately 50%. Surprisingly, a similar result could be achieved via introduction of RGS7 shRNA directly to the myocardium without impacting RGS7 levels in the liver directly. Indeed, doxorubicin-treated cardiomyocytes secrete the endocrine factors transforming growth factor ß1 (TGFß1) and TGFß superfamily binding protein follistatin-related protein 1 (FSTL1). Importantly, RGS7 overexpression in the heart was sufficient to recapitulate the impacts of doxorubicin on the liver and inhibition of TGFß1 signaling with the receptor blocker GW788388 ameliorated the effect of cardiac RGS7 overexpression on hepatic fibrosis, steatosis, oxidative stress, and cell death as well as the resultant elevation in liver enzymes. Together these data demonstrate that RGS7 controls both the release of TGFß1 from the heart and the profibrotic and pro-oxidant actions of TGFß1 in the liver and emphasize the functional significance of endocrine cardiokine signaling in the pathogenesis of chemotherapy drive multiorgan damage.