The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.

Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism.

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Background Patients in Yemen commonly visit community pharmacies to obtain consultation or treatment for common ailments. Community pharmacists have an opportunity to optimize medication use and improve patient outcomes. This study aimed to evaluate the attitudes and practices of community pharmacists regarding their participation in public health activities and barriers to their participation in these activities. Methods This cross-sectional study was carried out among community pharmacists working in pharmacies located in urban areas of the Aden governorate of Yemen from March to June 2017 using a self-administered questionnaire. We selected pharmacies from a line list using proportional sampling according to the number of pharmacies in the urban areas of each district. The questionnaire contained four sections: demographic characteristics, attitudes, practices, and barriers encountered. Data were analyzed descriptively, and the Chi-square test was used for analyzing the association of variables (alpha = 0.05). Results The questionnaire was distributed to 200 community pharmacists working in community pharmacies. Of the 200 respondents, 62% ( n = 124) were male. Overall, the mean age (sd) was 30.0 years (8.6) with the number of years of work experience between 2 and 9.9 years ( n = 158, 79%). On average, 62.3% of the pharmacists had a positive attitude toward participation in public health activities. Providing education to stop tobacco chewing, smoking, alcohol drinking and improve oral hygiene was an important activity of the community pharmacists. Blood pressure measurements (86%, n = 172) and glucose tests (45%, n = 90) were commonly conducted for clients. Lack of time (71%, n = 142) and lack of teamwork (70%, n = 140) were mentioned as common barriers to participation in public health activities. Conclusions Community pharmacists had a positive attitude toward public health activities. Health education and routine health tests were important practices of the community pharmacists. Barriers need to be overcome to enable more active participation by community pharmacists in public health activities by consulting with all stakeholders, assessing the situation, considering alternatives and taking action. Electronic supplementary material The online version of this article (10.1186/s12913-019-4133-y) contains supplementary material, which is available to authorized users.

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