The human body requires energy to function. Adenosine triphosphate (ATP) is the cellular currency for energy-requiring processes including mechanical work (i.e., exercise). ATP used by the cells is ultimately derived from the catabolism of energy substrate molecules—carbohydrates, fat, and protein. In prolonged moderate to high-intensity exercise, there is a delicate interplay between carbohydrate and fat metabolism, and this bioenergetic process is tightly regulated by numerous physiological, nutritional, and environmental factors such as exercise intensity and duration, body mass and feeding state. Carbohydrate metabolism is of critical importance during prolonged endurance-type exercise, reflecting the physiological need to regulate glucose homeostasis, assuring optimal glycogen storage, proper muscle fuelling, and delaying the onset of fatigue. Fat metabolism represents a sustainable source of energy to meet energy demands and preserve the ‘limited’ carbohydrate stores. Coordinated neural, hormonal and circulatory events occur during prolonged endurance-type exercise, facilitating the delivery of fatty acids from adipose tissue to the working muscle for oxidation. However, with increasing exercise intensity, fat oxidation declines and is unable to supply ATP at the rate of the exercise demand. Protein is considered a subsidiary source of energy supporting carbohydrates and fat metabolism, contributing to approximately 10% of total ATP turnover during prolonged endurance-type exercise. In this review we present an overview of substrate metabolism during prolonged endurance-type exercise and the regulatory mechanisms involved in ATP turnover to meet the energetic demands of exercise.

Background: There are various factors that play a major role in influencing the overall health conditions of women diagnosed with breast cancer. The population of women in Makkah region are diverse, therefore it is significant to highlight the possible determinants of breast cancer in this population. This is a case-control study that assessed determinants of breast cancer including socioeconomic factors, health-related characteristics, menstrual histories and breastfeeding among postmenopausal women in Makkah region in Saudi Arabia.Methods: A total of 432 female participants (214 cases and 218 controls) were recruited for this study. A validated questionnaire was completed by trained dietitians at King Abdullah Medical City Hospital in the Makkah region of Saudi Arabia.Results: Results displayed that determinants of breast cancer were associated significantly (P < 0.05) with unemployment, large family size, lack of knowledge and awareness about breast cancer, obesity, sedentary lifestyle, smoking, starting menarche at an early age, as well as hormonal and non-hormonal contraceptive use. There was no effect of diabetes, hypertension, hyperlipidemia, and duration of breastfeeding on the incidence of breast cancer.Conclusion: In summary, the results of this study accentuate the possible effect of socioeconomic factors, health-related characteristics and menstrual history on the incidence of breast cancer in postmenopausal women in the Makkah region. Education programs should be applied to increase breast cancer awareness and possibly decrease its incidence.

Chemoresistance to 5-fluorouracil (5-FU) is common during colorectal cancer (CRC) treatment. This study measured the chemotherapeutic effects of 5-FU, active vitamin D₃ (VD₃), and/or metformin single/dual/triple regimens as complementary/alternative therapies. Ninety male mice were divided into: negative and positive (PC) controls, and 5-FU, VD₃, Met, 5-FU/VD₃, 5-FU/Met, VD₃/Met, and 5-FU/VD₃/Met groups. Treatments lasted four weeks following CRC induction by azoxymethane. Similar regimens were also applied in the SW480 and SW620 CRC cell lines. The PC mice had abundant tumours, markedly elevated proliferation markers (survivin/CCND1) and PI3K/Akt/mTOR, and reduced p21/PTEN/cytochrome C/caspase-3 and apoptosis. All therapies reduced tumour numbers, with 5-FU/VD₃/Met being the most efficacious regimen. All protocols decreased cell proliferation markers, inhibited PI3K/Akt/mTOR molecules, and increased proapoptotic molecules with an apoptosis index, and 5-FU/VD₃/Met revealed the strongest effects. In vitro, all therapies equally induced G1 phase arrest in SW480 cells, whereas metformin-alone showed maximal SW620 cell numbers in the G0/G1 phase. 5-FU/Met co-therapy also showed the highest apoptotic SW480 cell numbers (13%), whilst 5-FU/VD₃/Met disclosed the lowest viable SW620 cell percentages (81%). Moreover, 5-FU/VD₃/Met revealed maximal inhibitions of cell cycle inducers (CCND1/CCND3), cell survival (BCL2), and the PI3K/Akt/mTOR molecules alongside the highest expression of cell cycle inhibitors (p21/p27), proapoptotic markers (BAX/cytochrome C/caspase-3), and PTEN in both cell lines. In conclusion, metformin monotherapy was superior to VD₃, whereas the 5-FU/Met protocol showed better anticancer effects relative to the other dual therapies. However, the 5-FU/VD₃/Met approach displayed the best in vivo and in vitro tumoricidal effects related to cell cycle arrest and apoptosis, justifiably by enhanced modulations of the PI3K/PTEN/Akt/mTOR pathway.

Chronic kidney disease, one of the most common diseases in the world, is characterized by irreversible impairment of the kidney’s metabolic, excretory, and endocrine functions. During end-stage renal disease, patients require renal replacement therapy, such as hemodialysis (HD). Protein-energy wasting is a common health problem among HD patients. This study aims to assess the nutritional status of HD patients at two HD centers in Jeddah, Saudi Arabia, and to determine its associated factors. A cross-sectional study was conducted at two different dialysis centers in Jeddah, Saudi Arabia; 211 female and male HD patients. Malnutrition was recognized using the modified-subjective global assessment (M-SGA) comprising two parts: medical history and physical examination. Sociodemographic and health status for all patients were also determined. Patients were classified based on their M-SGA score into two groups: normal and malnourished. Overall, 54.5% of the participants showed malnutrition. Unemployment, low muscle strength and mass, high level of medication use, and high dialysis vintage were positively (P < .05) associated with malnutrition. In conclusion, the M-SGA score indicates a high prevalence of malnutrition among HD patients. These results show the importance of regular assessment and follow-ups for HD patients ensuring better health and nutritional status.

Background: The Biarum species (Kardeh) has been consumed as a traditional functional food and medicine for decades. The current study investigates the phytochemistry, in-vitro and in-vivo bioactivities of methanol extracts of B. bovei. Methods: The Gas-chromatography mass spectrophotometer (GS/GS-MS) was used to analyze the phytochemical profile of the methanol extracts of B. bovei leaves and corms. The B. bovei extracts (BBE) were also investigated for in-vitro antioxidant, anticancer, and in-vivo acute toxicity (2000 mg/kg) activities. Results: The chemical profiling of BBE revealed mainly fatty acids, phytosterol, alcohols, and hydrocarbon compounds. Namely, Linoleic acid, eliadic acid, palmitic acid, 22,23-dihydro-stigmasterol, and campesterol. The antioxidant activity of BBE ranged between 0.24–3.85 μg TE/mL based on different assays. The extracts also exhibited significant anticancer activity against DU-145 (prostate cancer cells), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical cancer) cell lines with IC ₅₀ values ranging between 22.73–44.24 μg/mL. Rats fed on 2000 mg/kg dosage of BBE showed absence of any toxicological sign or serum biochemical changes. Conclusion: The detected phytochemicals and bioactivities of BBE scientifically backup the folkloric usage as an important source of nutraceuticals and alternative medicine for oxidative stress-related diseases and carcinogenesis inhibition.