Integrative systems-level analysis reveals a contextual crosstalk between hypoxia and global metabolism in human breast tumors.

Hypoxia is known to induce reprogramming of glucose metabolism in cancer. However, the impact of hypoxia on global metabolism remains poorly understood. Here, using the systems approach, we evaluated the potential crosstalk between hypoxia and global metabolism using data from > 2000 breast tumors.

Withaferin A decreases glycolytic reprogramming in breast cancer.

Reprogrammed glucose metabolism is considered as the hallmark of cancer with therapeutic implications. Phytocompounds have potential to inhibit cancer metabolism. Here, we tested the ability of Withaferin A (WA), a withanolide derived from Withania somnifera, in modulating cancer metabolism.

A critical review of sustainable application of biochar for green remediation: Research uncertainty and future directions.

Biochar, a carbon-rich material produced from the pyrolysis of organic biomass, has gained significant attention as a potential solution for sustainable green remediation practices. Several studies analyze biomass-derived biochar techniques and environmental applications, but comprehensive assessments of biochar limitations, uncertainty, and future research directions still need to be improved. This critical review aims to present a comprehensive analysis of biochar's efficacy in environmental applications, including soil, water, and air, by sequentially addressing its preparation, application, and associated challenges.

HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability.

Unlabelled: The molecular basis of human papillomavirus (HPV)-mediated cellular immortalization and malignant transformation has illustrated an indispensable role of viral E6/E7-oncoproteins. However, the impact of viral-oncoproteins on the metabolic phenotype of cancer cells remains ambiguous. We showed silencing of HPV18-encoded E6/E7-oncoprotein significantly reduced glucose consumption, lactate production, ATP level and viability.

Identification of plant-based hexokinase 2 inhibitors: combined molecular docking and dynamics simulation studies.

Cancer cells ferment glucose, even under aerobic conditions, following a phenomenon known as the 'Warburg effect.' Hexokinase 2 (HK2) catalyzes the crucial step of phosphorylation of glucose for subsequent utilization in glycolysis and other pathways. HK2 has been proposed as a potential therapeutic target for anti-cancer therapy because of its enhanced expression in glucose-dependent tumors.

Phytocompounds Targeting Metabolic Reprogramming in Cancer: An Assessment of Role, Mechanisms, Pathways, and Therapeutic Relevance.

The metabolism of cancer is remarkably different from that of normal cells and confers a variety of benefits, including the promotion of other cancer hallmarks. As the rewired metabolism is a near-universal property of cancer cells, efforts are underway to exploit metabolic vulnerabilities for therapeutic benefits. In the continued search for safer and effective ways of cancer treatment, structurally diverse plant-based compounds have gained substantial attention.

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer.

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence.

Macroeconomic impacts of cigarette consumption in Pakistan.

Background: Pakistan has a large population of tobacco users, with about 24 million adults consuming tobacco products in one form or another. There is a dearth of research on the impact of a reduction in tobacco use on Pakistan's economy which can inform policy-makers on the extent that tobacco control measures would affect macroeconomic indicators such as output and employment.

Objectives: The objective of this study is to quantify the changes in output, income and employment resulting from changes in cigarette consumption and to quantify the impact of such changes on the overall economy.

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India.

Background: Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer.

Methods: Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue.

MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance.

Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis.

Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition.

Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis.

Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer.

Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The characteristic increase in glycolysis, i.e.

Pyruvate kinase M knockdown-induced signaling via AMP-activated protein kinase promotes mitochondrial biogenesis, autophagy, and cancer cell survival.

Preferential expression of the low-activity (dimeric) M2 isoform of pyruvate kinase (PK) over its constitutively active splice variant M1 isoform is considered critical for aerobic glycolysis in cancer cells. However, our results reported here indicate co-expression of PKM1 and PKM2 and their possible physical interaction in cancer cells. We show that knockdown of either PKM1 or PKM2 differentially affects net PK activity, viability, and cellular ATP levels of the lung carcinoma cell lines H1299 and A549.

Decreased expression of MGMT in correlation with aberrant DNA methylation in esophageal cancer patients from North India.

O-6-methylguanine-DNA methyltransferase, DNA repair gene, has been found to be involved with the pathogenesis of the esophageal cancer. DNA hypermethylation and other factors have been suggested to downregulate O-6-methylguanine-DNA methyltransferase. In this communication, the methylation status of O-6-methylguanine-DNA methyltransferase gene and the corresponding O-6-methylguanine-DNA methyltransferase protein expression in esophageal cancer from North India has been studied.

WITHDRAWN: Regulation of Pyruvate Kinase M Switch towards PKM1 by LKB1-AMPK Axis Tolerates Hypoglycemic Stress in Cancer Cells.

This article has been withdrawn by the authors. The PKM2 immunoblot in Fig 2E was reused as part of the Caspase-3 immunoblot in Fig 9C. The PKM2 immunoblot from 5 mM Glu, fractions 1-10 was reused as the PKM2 immunoblot from 1 mM Glu, fractions 1-10.

ERK2-Pyruvate Kinase Axis Permits Phorbol 12-Myristate 13-Acetate-induced Megakaryocyte Differentiation in K562 Cells.

Metabolic changes that contribute to differentiation are not well understood. Overwhelming evidence shows the critical role of glycolytic enzyme pyruvate kinase (PK) in directing metabolism of proliferating cells. However, its role in metabolism of differentiating cells is unclear.

Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy.

Resveratrol has been shown to exhibit its anti-cancer effect through a variety of mechanisms. Here, TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) was identified as an important target of resveratrol for exhibiting ROS-dependent-consequences on apoptosis and autophagy. Resveratrol treatment decreased TIGAR protein irrespective of cell line used.

Generation of sub-ppb level vapor phase mixtures of biogenic volatile organic compounds from liquid phase standards and stepwise characterization of their volatilization properties by thermal desorption-gas chromatography-mass spectrometry.

In the analysis of biogenic volatile organic compounds (BVOCs) in ambient air, preparation of a sub-ppb level standard is an important factor. This task is very challenging as most BVOCs (e.g.

Monoterpenes released from fruit, plant, and vegetable systems.

To quantify the emission rate of monoterpenes (MTs) from diverse natural sources, the sorbent tube (ST)-thermal desorption (TD) method was employed to conduct the collection and subsequent detection of MTs by gas chromatography. The calibration of MTs, when made by both mass spectrometric (MS) and flame ionization detector (FID), consistently exhibited high coefficient of determination values (R2 > 0.99).

An assessment of the liquid-gas partitioning behavior of major wastewater odorants using two comparative experimental approaches: liquid sample-based vaporization vs. impinger-based dynamic headspace extraction into sorbent tubes.

The gas-liquid partitioning behavior of major odorants (acetic acid, propionic acid, isobutyric acid, n-butyric acid, i-valeric acid, n-valeric acid, hexanoic acid, phenol, p-cresol, indole, skatole, and toluene (as a reference)) commonly found in microbially digested wastewaters was investigated by two experimental approaches. Firstly, a simple vaporization method was applied to measure the target odorants dissolved in liquid samples with the aid of sorbent tube/thermal desorption/gas chromatography/mass spectrometry. As an alternative method, an impinger-based dynamic headspace sampling method was also explored to measure the partitioning of target odorants between the gas and liquid phases with the same detection system.

Dominant negative mutations affect oligomerization of human pyruvate kinase M2 isozyme and promote cellular growth and polyploidy.

This study was designed to understand the mechanism and functional implication of the two heterozygous mutations (H391Y and K422R) of human pyruvate kinase M2 isozyme (PKM(2)) observed earlier in a Bloom syndrome background. The co-expression of homotetrameric wild type and mutant PKM(2) in the cellular milieu resulting in the interaction between the two at the monomer level was substantiated further by in vitro experiments. The cross-monomer interaction significantly altered the oligomeric state of PKM(2) by favoring dimerization and heterotetramerization.

Time to ambulation after hip fracture surgery: relation to hospitalization outcomes.

Objective: To test the hypothesis: Time to ambulation (walking) after hip fracture surgery impacts the frequency of postoperative complications and length of hospital stay.

Methods: A retrospective observational study of a cohort of all patients admitted to a university teaching hospital with a principal International Classification of Diseases-9 diagnosis of a hip fracture during 3 calendar years.

Results: A total of 131 participants were identified (68% were aged 65 years or older).