Drug induced nutrient insufficiency

The major reason for multidrug resistance is the failure of chemotherapy in many tumors, including colon cancer. Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor that simulates multiple cellular response to hypoxia. HIF-1α has been known to play a vital role towards tumor resistance; however, its mechanism of action is still not fully elucidated. N this study, we found that HIF-1α remarkably modulated drug resistance-associated proteins upon CopA3 peptide treatment against colon cancer cells...

Alcohol and drug overdoses cause liver diseases such as cirrhosis, hepatitis, and liver cancer globally. In particular, an overdose of acetaminophen (APAP), which is generally used as an analgesic and antipyretic agent, is a major cause of acute hepatitis, and cases of APAP-induced liver damage are steadily increasing. Potential antioxidants may inhibit the generation of free radicals and prevent drug-induced liver damage. Among plant-derived natural materials, radishes (RJ) and turnips (RG) have anti-inflammatory, anticancer, and antioxidant properties due to the presence of functional ingredients, such as glucosinolate and isothiocyanate...

Kidney organoids derived from human induced pluripotent stem cells (iPSCs) have proven to be a valuable tool to study kidney development and disease. However, the lack of vascularization of these organoids often leads to insufficient oxygen and nutrient supply. Vascularization has previously been achieved by implantation into animal models, however, the vasculature arises largely from animal host tissue. Our aim is to transition from an in vivo implantation model towards an in vitro model that fulfils the advantages of vascularization whilst being fully human-cell derived...

Hypoxia, or insufficient oxygen availability is a common feature in the development of a myriad of cardiovascular-related conditions including ischemic disease. Hydrogen sulphide (H2 S) donors, such as sodium thiosulphate (STS), are known for their cardioprotective properties. However, H2 S due to its gaseous nature, is released and cleared rapidly, limiting its potential translation to clinical settings. For the first time, we developed and characterised liposome formulations encapsulating STS and explored their potential for modulating STS uptake, H2 S release and the ability to retain pro-angiogenic and biological signals in a hypoxia-like environment mirroring oxygen insufficiency in vitro...

OBJECTIVE: The aim: To explore the possibilities of rationalizing antibacterial therapy by comparative analysis of the accumulation of ceftriaxone administered lymphotropically and intramuscularly. PATIENTS AND METHODS: Materials and methods: The research used a method of studying the sensitivity of microorganisms to antibacterial drugs, which is based on the diffusion of antibacterial drugs from the carrier (homogenate of the test organ) in a dense nutrient medium, which, depending on the sensitivity of microorganisms, inhibits the growth of the studied culture and is accompanied by the formation of a growth inhibition zone (GIZ) in the nutrient medium...

Currently used antidepressants do not always provide the desired results, and many patients suffer from treatment-resistant depression. Clinical studies suggest that zinc deficiency (ZnD) may be an important risk factor for depression and might blunt the effect of antidepressants. This study aimed to examine whether ZnD might blunt the effectiveness of antidepressants in the olfactory bulbectomy model (OB) of depression in rats. For this purpose, rats were subjected to the OB model, fed a zinc-deficient diet (3 mg Zn/kg) for 3 weeks, and finally treated with escitalopram (Esc), venlafaxine (Ven) 10 mg/kg, i...

During its fourth transporter workshop in 2021, the International Transporter Consortium (ITC) provided updates on emerging clinically relevant transporters for drug development. Previously highlighted and new transporters were considered based on up-to-date clinical evidence of their importance in drug-drug interactions and potential for altered drug efficacy and safety, including drug-nutrient interactions leading to nutrient deficiencies. For the first time, folate transport pathways (PCFT, RFC, and FRα) were examined in-depth as a potential mechanism of drug-induced folate deficiency and related toxicities (e...

Autophagy is a catabolic process in which an organism responds to its nutrient or metabolic emergencies. It involves the degradation of cytoplasmic proteins and organelles by forming double-membrane vesicles called "autophagosomes." They sequester cargoes, leading them to degradation in the lysosomes. Although autophagy acts as a protective mechanism for maintaining homeostasis through cellular recycling, it is ostensibly a cause of certain cancers, but a cure for others. In other words, insufficient autophagy, due to genetic or cellular dysfunctions, can lead to tumorigenesis...

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2 O2 ). Also, single starvation therapy shows limited ability on resisting tumors. The "metal-oxidase" cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a "starvation effect", but also provide CDT with sufficient H2 O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects...

Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway (PPP)...

Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells...

Most solid tumors, such as head and neck cancers, feature a hypoxic microenvironment due to angiogenic dysregulation and the consequent disruption of their vascular network. Such nutrient-deprived environment can induce genomic changes in several tumor cell populations, conferring survival and proliferative advantages to cancer cells through immunosuppression, metabolic switches and enhanced invasiveness. These transcriptional changes, together with the selective pressure hypoxia exerts on cancer cells, leads to the propagation of more aggressive and stress-resistant subpopulations increasing therapy resistance and worsening patient outcomes...

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts...

BACKGROUND: The placenta is the functional interface between the mother and the fetus during pregnancy, and a critical determinant of fetal growth and life-long health. In the first trimester, it develops under a low-oxygen environment, which is essential for the conceptus who has little defense against reactive oxygen species produced during oxidative metabolism. However, failure of invasive trophoblasts to sufficiently remodel uterine arteries toward dilated vessels by the end of the first trimester can lead to reduced/intermittent blood flow, persistent hypoxia and oxidative stress in the placenta with consequences for fetal growth...

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts...

Human cardiomyocytes (CMs) have potential for use in therapeutic cell therapy and high-throughput drug screening. Because of the inability to expand adult CMs, their large-scale production from human pluripotent stem cells (hPSC) has been suggested. Significant improvements have been made in understanding directed differentiation processes of CMs from hPSCs and their suspension culture-based production at chemically defined conditions. However, optimization experiments are costly, time-consuming, and highly variable, leading to challenges in developing reliable and consistent protocols for the generation of large CM numbers at high purity...

Nanoformulations offer the opportunity to overcome the shortcomings of drug molecules such as low solubility, side effects, insufficient stability and etc. but in the most of the current nanomedicines, nanocarriers as excipients do not directly participate in the therapy procedure. Accordingly, it is promising to develop the nanotherapeutics composed entirely of pharmaceutically active molecules. Tea polyphenols, especially epigallocatechin gallate (EGCG), are a kind of natural antioxidants with the varied biological and healthy beneficial effects, and are extensively investigated as nutrients and anticancer drugs...

Diabetes Mellitus is a common metabolic or endocrine disorder that occurs as a result of insufficient amounts of insulin secretion or defect in the action of insulin produced from pancreatic beta cells. Antioxidant containing food items are very effective in reducing complications that arise due to diabetes, indicating that it may be beneficial for treating metabolic disorders. In this study, we used some essential nutrients enriched with glutathione, named as Glothione (GN), and evaluated the antidiabetic effect of GN in alloxan-induced diabetic rats...

Cancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2...

BACKGROUND: The classification of dietary supplements as foodstuffs promotes widespread access to them and increases the possibility of patients using them without being monitored. Unreasonable or excessive consumption of these preparations poses risks to type-2 diabetes mellitus (T2DM) patients (among others) because it may induce disturbances in glycemic control. The aim of this study was to assess the frequency of dietary supplementation among patients using anti-diabetic drugs and such patients' nutrient intake in order to evaluate the potential risk of interactions...