Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents.

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are of limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver cancer initiation, thus providing a new way to combat liver cancer. Ferroptosis is a distinct form of controlled cell death that differs from conventional cell death routes like apoptosis, necrosis, and pyroptosis. It results from intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads to the accumulation of lipid peroxides that further result in oxidative damage to cell membranes, disrupt normal functioning, and ultimately speed up the ferroptosis phenomenon. Ferroptosis regulation is intricately linked to cellular physiological processes, encompassing iron metabolism, lipid metabolism, and the equilibrium between oxygen-free radical reactions and lipid peroxidation. This review intends to summarize the natural compounds targeting ferroptosis in liver cancer to offer new therapeutic ideas for liver cancer. Furthermore, it serves as the foundation for identifying and applying chemical medicines and natural chemicals that target ferroptosis to treat liver cancer efficiently.

Correction: Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

A review on advances in green treatment of glycerol waste with a focus on electro-oxidation pathway.

Over the past decades, research efforts are being devoted into utilizing the biomass waste as a major source of green energy to maintain the economic, environmental, and social sustainability. Specifically, there is an emerging consensus on the significance of glycerol (an underutilised waste from biodiesel industry) as a cheap, non-toxic, and renewable source for valuable chemicals synthesis. There are numerous methods enacted to convert this glycerol waste to tartronic acid, mesoxalic acid, glyceraldehyde, dihydroxyacetone, oxalic acid and so on. Among these, the green electro-oxidation technique is one of the techniques that possesses potential for industrial application due to advantages such as non-toxicity process, fast response, and lower energy consumption. The current review covers the general understanding on commonly used techniques for alcohol (C1 & C2) conversion, with a specific insight on glycerol (C3) electro-oxidation (GOR). Since catalysts are the backbone of chemical reaction, they are responsible for the overall economy prospect of any processes. To this end, a comprehensive review on catalysts, which include noble metals, non-noble metals, and non-metals anchored over various supports are incorporated in this review. Moreover, a fundamental insight into the development of future electrocatalysts for glycerol oxidation along with products analysis is also presented.

Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds.

OBJECTIVE: To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing. METHODS: Mixtures of acetonitrile and water with acetonitrile content between 95% and 50% v/v in 5% increments were kept separately in 10 different chromatographic chambers, saturated with solvent for 2 h. Spots were observed under UV light at λ=254 nm p-anisaldehyde used as a spraying reagent. Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps. For percentage wound contraction, five groups of animal (mice) (25-30 g) of either sex were selected. Wound were created on dorsal surface of animals using toothed forceps, scalpel and pointed scissors. The wound areas were calculated using vernier caliper. After making wound mice were orally administered 35 mg/kg 6-shogoal, 6-gingerol, 8-gingerol and 10-gingerol respectively. Group E as the control group received tap water. RESULTS: The lipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis. Significant correlations were found between log P values calculated by software program and the experimental reversed-phase thin-layer chromatography data. Order of wound healing property of ginger compounds is directly dependent on lipophilicity i.e. more lipophilic compound has highest activity. CONCLUSIONS: Experimentally determined lipophilicity (R MO) values were correlated with log P determined by software's and found satisfactory. Lipophilicity (R MO) is a useful parameter for the determination and prediction of biological activity of ginger compounds.

Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds

<p><b>OBJECTIVE</b>To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing.</p><p><b>METHODS</b>Mixtures of acetonitrile and water with acetonitrile content between 95% and 50% v/v in 5% increments were kept separately in 10 different chromatographic chambers, saturated with solvent for 2 h. Spots were observed under UV light at λ=254 nm p-anisaldehyde used as a spraying reagent. Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps. For percentage wound contraction, five groups of animal (mice) (25-30 g) of either sex were selected. Wound were created on dorsal surface of animals using toothed forceps, scalpel and pointed scissors. The wound areas were calculated using vernier caliper. After making wound mice were orally administered 35 mg/kg 6-shogoal, 6-gingerol, 8-gingerol and 10-gingerol respectively. Group E as the control group received tap water.</p><p><b>RESULTS</b>The lipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis. Significant correlations were found between log P values calculated by software program and the experimental reversed-phase thin-layer chromatography data. Order of wound healing property of ginger compounds is directly dependent on lipophilicity i.e. more lipophilic compound has highest activity.</p><p><b>CONCLUSIONS</b>Experimentally determined lipophilicity (R MO) values were correlated with log P determined by software's and found satisfactory. Lipophilicity (R MO) is a useful parameter for the determination and prediction of biological activity of ginger compounds.</p>

Viscosity mixing rules for binary systems containing one ionic liquid.

In this work the applicability of four of the most commonly used viscosity mixing rules to [ionic liquid (IL)+molecular solvent (MS)] systems is assessed. More than one hundred (IL+MS) binary mixtures were selected from the literature to test the viscosity mixing rules proposed by 1) Hind (Hi), 2) Grunberg and Nissan (G-N), 3) Herric (He) and 4) Katti and Chaudhri (K-C). The analyses were performed by estimating the average (absolute or relative) deviations, AADs and ARDs, between the available experimental data and the predicted ideal mixture viscosity values obtained by means of each rule. The interaction terms corresponding to the adjustable parameters inherent to each rule were also calculated and their trends discussed.

Beta-2 adrenergic receptor genotypes and haplotypes in different ethnic groups.

The human beta-2 adrenergic receptor (beta2AR) is responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists. Three functional polymorphisms in codons 16, 27 and 164 have been described which have clinical importance for several diseases, including asthma, hypertension, heart failure, cystic fibrosis and obesity, as well as response to beta-agonist therapy. These were evaluated in 726 individuals from 8 distinct ethnic populations (Chinese, Filipino, Southwest Asian, Saudi, Ghanaian, Kenyan, Sudanese, and European from Scotland). The results show that most haplotypes are shared among all populations, yet there are marked differences in their frequency distributions geographically. The genetic distance tree is different from standard human population distance trees, implying a different mode of evolution for this locus than that for human population gene-flow history. The multilocus frequency differences between the observed clusters of populations correspond to historical haplotype groupings that have been found to be functionally different with respect to multiple medically related phenotypes. Further studies are needed to see if functional relationships are the same across populations.

Fluconazole improves survival in septic shock: a randomized double-blind prospective study.

OBJECTIVE: To demonstrate whether fluconazole reduces multiple organ failure and mortality in early septic shock (<24 hrs). DESIGN: A prospective randomized double-blind study. SETTING: A medical and surgical adult intensive care unit in a tertiary referral center. PATIENTS: Values were obtained from 71 general adult intensive care unit patients. INTERVENTIONS: During a 2.5-yr period, December 1998-June 2001, 71 patients with septic shock attributed to either nosocomial pneumonia (n = 37) or intra-abdominal sepsis (n = 34) were admitted to our intensive care unit and met the criteria of early septic shock and were entered into this study. All patients were randomized by our clinical pharmacist to receive daily either 200 mg of fluconazole in isotonic saline (fluconazole group = 32) or isotonic saline alone (placebo group = 39) intravenously during the course of their septic shock. MEASUREMENTS AND MAIN RESULTS: All patients were closely monitored with pulmonary artery catheters and parameters to calculate daily organ dysfunction and Acute Physiology and Chronic Health Evaluation II scores. There was a highly significant increase in 30-day survival in the fluconazole-treated patients compared with the placebo patients (78% vs. 46%). However, fluconazole was found to be more effective in patients with septic shock attributed to intra-abdominal sepsis than to nosocomial pneumonia. Increased survival in the intra-abdominal sepsis clinical category was mirrored by a significantly lower number of organ failures in the treated group compared with the placebo group whereas the number of organ failures in the fluconazole group attributed to nosocomial pneumonia were not significantly increased compared with the control group. The septic shock state was considered in all cases to be attributed to bacterial and not to disseminated yeast infection with the exception of one patient in the control group who was admitted with candidemia. The mechanisms by which fluconazole exerts its protective effect against septic shock in patients is far from clear. However, fluconazole has been shown to enhance bactericidal activity of neutrophils and also to inhibit transmigration and adhesion of neutrophils in capillaries of distant organs. CONCLUSIONS: The development of organ failure and mortality in septic shock was significantly reduced by fluconazole given intravenously. The mechanism of action of fluconazole in reducing multiple organ dysfunction in this group of patients may be attributed to the ability of fluconazole to increase recruitment, improve bactericidal activity of neutrophils, and to contain microorganisms locally.

Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer.

HER-2, a protooncogene located on chromosome 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity. Alterations of the HER-2 gene have been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors. It is also a cancer-therapeutic target for antibody-based therapy against the HER-2 protein. A single-nucleotide polymorphism (SNP) at codon 655, resulting in a G-to-A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer, particularly among younger women. To understand the importance of this finding throughout the world, we evaluated this polymorphism in Ghanaian, Kenyan, Sudanese, Caucasian, African-American, Saudi, and Filipino subjects using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the Val allele, which is associated with increased breast cancer risk, was highly variable between populations (0%-24%). Continental African populations had a lower frequency of the Val allele than did Saudi, Chinese, Filipino, Caucasian, and African-American subjects. The data suggest that this SNP has variable frequency in different ethnic groups. The findings in this study correspond with the lower incidence and lower risk of breast cancer in African women compared with Caucasian and African-American women.