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.

Molecular mechanisms of alcohol's effects on the human body: A review and update.

Alcohol consumption has been linked to numerous negative health outcomes although it has some beneficial effects on moderate dosages, the most severe of which being alcohol-induced hepatitis. The number of people dying from this liver illness has been shown to climb steadily over time, and its prevalence has been increasing. Researchers have found that alcohol consumption primarily affects the brain, leading to a wide range of neurological and psychological diseases. High-alcohol-consumption addicts not only experienced seizures, but also ataxia, aggression, social anxiety, and variceal hemorrhage that ultimately resulted in death, ascites, and schizophrenia. Drugs treating this liver condition are limited and can cause serious side effects like depression. Serine-threonine kinases, cAMP protein kinases, protein kinase C, ERK, RACK 1, Homer 2, and more have all been observed to have their signaling pathways disrupted by alcohol, and alcohol has also been linked to epigenetic changes. In addition, alcohol consumption induces dysbiosis by changing the composition of the microbiome found in the gastrointestinal tract. Although more studies are needed, those that have been done suggest that probiotics aid in keeping the various microbiota concentrations stable. It has been argued that reducing one's alcohol intake may seem less harmful because excessive drinking is a lifestyle disorder.

Letrozole: Pharmacology, toxicity and potential therapeutic effects.

The highly active estrogen metabolism and receptor protein expression are to blame for the elevated breast cancer (BC) rate in post-menopausal women. Letrozole is a powerful endocrine medication that targets and inhibits the aromatase, often known as an aromatase inhibitor (AI). It aids in the adjuvant, neoadjuvant, and metastatic treatment of HR+ breast cancer because it can boost FSH production for ovulation induction. It has recently been used in infertile pre-menopausal women. The main advantages of utilizing letrozole to enhance follicle development may be wasted in current infertility treatments. We went into great length in this review about the pharmacokinetics, pharmacodynamics, and distinct adverse effects of the drug on the heart, kidney, liver, embryo, bone, and ovary. It also causes apoptosis, necrosis, and fibrosis, which all result in the demise of cancer cells. Its central and peripheral effects on follicle formation, estrogen production in the ovaries, and their clinical implications are explored in detail in this work.

Hesperidin and hesperetin against heavy metal toxicity: Insight on the molecular mechanism of mitigation.

Toxic heavy metals (THMs) are non-essential hazardous environmental pollutants with intractable health challenges in humans and animals. Exposure to lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr) are ubiquitous and unavoidable due to food contamination, mining, and industrial mobilization. They are triggers of tissue impairment and aberrant signaling pathways that cascade into several toxicities and pathologies. Each of Pb, Cd, Hg, As, Ni, and Cr aggravate oxidative inflammation, protein dysregulation, apoptotic induction, DNA damage, endocrine deficits, and mitochondrial dysfunction contributing to the pathophysiology of diseases. Hesperidin (HSD) and hesperetin (HST) are flavonoids from citrus fruits, and systematic investigations suggest their potential to combat the molecular alterations and toxicities induced by THMs. They mitigate heavy metal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic effects via scavenging free radicals and modulation of ATPases, cell cycle proteins, and various cellular signaling pathways, including Nrf2/HO-1/ARE, PI3K/mTOR/Akt, MAPK/caspase-3/Bax/Bcl-2, iNOS/NF-κB/TNF-α/COX-2. This review summarized the mechanistic effects of heavy metal toxicity and the insights on molecular mechanisms underlying mitigation of heavy metal toxicity by HSD and HST. Hesperidin and hesperetin are potential flavonoids for the modulation of pathological signaling networks associated with THMs. Therefore, HSD and HST can be suggested as natural dietary agents and blockers of harmful effects of THMs.

Mechanism of chromium-induced toxicity in lungs, liver, and kidney and their ameliorative agents.

Heavy metal Chromium (Cr), can adversely affect humans and their health if accumulated in organs of the body, such as the lungs, liver, and kidneys. Cr (VI) is highly toxic and has a higher solubility in water than Cr (III). One of the most common routes for Cr exposure is through inhalation and is associated with liver, lung, kidney damage, widespread dermatitis, GI tract damage, human lung cancer, cardiomyopathies, and cardiovascular disease. The increase in ROS production has been attributed to most of the damage caused by Cr toxicity. Cr-induced ROS-mediated oxidative stress has been seen to cause a redox imbalance affecting the antioxidant system balance in the body. The Nrf2 pathway dysregulation has been implicated in the same. Deregulation of histone acetylation and methylation has been observed, together with gene methylation in genes such as p16, MGMT, APC, hMLH1, and also miR-143 repression. Several ultra-structural changes have been observed following Cr (VI)-toxicity, including rough ER dilation, alteration in the mitochondrial membrane and nuclear membrane, pycnotic nuclei formation, and cytoplasm vacuolization. A significant change was observed in the metabolism of lipid, glucose, and the metabolism of protein after exposure to Cr. Cr-toxicity also leads to immune system dysregulations with changes seen in the expression of IL-8, IL-4, IgM, lymphocytes, and leukocytes among others. P53, as well as pro-and anti-apoptotic proteins, are involved in apoptosis. These Cr-induced damages can be alleviated via agents that restore antioxidant balance, regulate Nrf-2 levels, or increase anti-apoptotic proteins while decreasing pro-apoptotic proteins.

A review on modern and smart technologies for efficient waste disposal and management.

In the current scenario, the word waste management holds much importance in every individual's life. Pollution and the generation of vast waste quantities with no proper waste management process have become one of humanity's biggest threats. This review article provides a complete review of the innovative technologies currently employed to handle and dispose of the waste successfully. This work aims to include the different solid, liquid, gaseous, and radioactive waste management processes. The novel and improved plasma gasification concepts, transmutation, incineration, bio-refineries, microbial fuel cells (MFC) have been thoroughly explained. In addition, some new techniques like Mr. Trash Wheel and the Smart bin approach provide much hope of adequately managing waste. The work's novelty lies in adopting several successful methods of various countries for waste disposal and management. To incorporate or improve India'sIndia's same techniques and processes, we have to tackle the ever-increasing waste disposal problems and find economic and eco-friendly ways of waste management.

Molecular mechanism of heavy metals (Lead, Chromium, Arsenic, Mercury, Nickel and Cadmium) - induced hepatotoxicity - A review.

Heavy metals pose a serious threat if they go beyond permissible limits in our bodies. Much heavy metal's viz. Lead, Chromium, Arsenic, Mercury, Nickel, and Cadmium pose a serious threat when they go beyond permissible limits and cause hepatotoxicity. They cause the generation of ROS which in turn causes numerous injuries and undesirable changes in the liver. Epidemiological studies have shown an increase in the levels of such heavy metals in the environment posing a serious threat to human health. Epigenetic alterations have been seen in the event of exposure to such heavy metals. Apoptosis, caspase activation as well as ultrastructural changes in the hepatocytes have also been seen due to heavy metals. Inflammation involving TNF-alpha, pro-inflammatory cytokines, MAPK, ERK pathways have been seen in the event of heavy metal hepatotoxicity. All these have shown that these heavy metals pose a serious threat to human health in particular and the environment as a whole.

The role of Interleukin-4 in COVID-19 associated male infertility - A hypothesis.

COVID-19 is a present-day complex pandemic infection with unpredictable levels of morbidity and mortality in various global populations. COVID-19 is associated with the different comorbidities with its change in biological function such as causing heart dysfunction via deregulating ACE-2 receptor, gastrointestinal risk via causing vomiting, diarrhea, and abdominal pain, chronic kidney disease via proteinuria and hematuria, diabetes mellitus, liver injury via increasing ALT, AST and bilirubin level, lung injury, CNS risk, ocular risk, and cancer risk. In this, we are focused on the COVID-19 connected with male infertility. Some of the studies show that the patients of COVID-19 are associated with impaired spermatogenesis. Impaired spermatogenesis via COVID-19 decreases the level of testosterone by disturbing cytokines such as TNF-α, IL-4, IL-6, and IL-12 and further, attenuates the sperm count. COVID-19 is causing inflammation via TNF-α and interferons. IL-4 plays an eminent role in the activation of the JAK-STAT pathway and leads to the disturbing pro-inflammatory cytokine as well as further cause's male infertility. Th2 activates the IL-4 through IgG and IgE and mediates apoptosis with the triggering of STAT signaling. The activated STAT signaling augments Batf/Irf4, and the Bach2/Batf pathway. On the other hand, SARS-CoV-2 is activating the level of Th2 cells. So, we hypothesized that the augmented Th2 cells would disturb the level of IL-4, JAK-STAT signaling, Batf/Irf4, and Bach2/Batf pathway. The disturbed IL-4 decreases the level of the ACE-2 with the inflammation. This further leads to male infertility in COVID-19 patients. So, in this hypothesis, we focused on the role of IL-4 in COVID-19 patients associated with male infertility via Th2 cells and JAK-STAT signaling.

Role of TGF-ß signalling in PCOS associated focal segmental glomerulosclerosis.

Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys. Onset of FSGS may either be congenital or due to other disorders that affect the metabolism and normal kidney function. Both PCOS and FSGS appear to be associated with Transforming Growth Factor-ß (TGF-ß) signalling. Over-expression of TGF-ß may be due to the activation of the thrombospondin 1 (TSP1) gene, which increases the probability of developing renal disorders. Higher androgen levels in PCOS may also cause podocyte damage thus directly impacting development of FSGS. This article reviews the role of TGF-ß's in PCOS and FSGS and explores the inter-relationship between these two disorders.