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The role of thiamine in nervous tissue.

The possibility that thiamine (vitamin B1) has a role in nervous tissue that is independent of its well-documented coenzyme function is discussed. After reviewing the localization and metabolism of the vitamin and its phosphate esters, the effects of either thiamine deprivation or antimetabolites of thiamine on conduction and transmission, and the relationship between thiamine triphosphate and the genetic, neurological disease, subacute necrotizing encephalomyelopathy (Leigh's disease), it is suggested that despite the lack of hard evidence, it is likely that the vitamin possesses this alterna

Identification of genital tract markers in the human seminal plasma using an integrative genomics approach.

STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male geni

Proliferating tumor cells mimick glucose metabolism of mature human erythrocytes.

Mature human erythrocytes are dependent on anerobic glycolysis, i.e. catabolism (oxidation) of one glucose molecule to produce two ATP and t … ribose-5-phosphate isomerase; RPE: ribulose 5-phosphate 3-epimerase; X5P: xylulose 5-phosphate; TK: transketolase; TA: transaldolase; F6P: fructose-6-phosphate; AR2: aldose reductase 2; SD: sorbitol dehydrogenase; HK: hexokinase; MG: mehtylglyoxal; DHAP: dihydroxyacetone phosphate; TILs: tumor-infiltrating lymphocytes; MCTs: monocarboxylate transporters; pHi: i …

Differential epithelial and stromal protein profiles in keratoconus and normal human corneas.

The purpose of the study was to identify epithelial and stromal proteins that exhibit up- or down-regulation in keratoconus (KC) vs. normal … ein, keratin type I cytoskeletal 16 and protein S100-A4) exhibited up-regulation and five proteins (transketolase, pyruvate kinase, 14-3-3 sigma isoform, phosphoglycerate kinase 1, and NADPH dehydrogenase (quinone) 1) showed down-regulation. A similar relative analysis showed that three KC stromal proteins (decorin, vimentin and keratocan) were up-regulated and …

Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfot

Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula.

OBJECTIVE: Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Isr … onsisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, …

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

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… Recent studies demonstrated that the transketolase family consists of the transketolase gene and two transketolase‐like (TKTL) genes, TKTL1 and TKTL2. … Transketolase family members are overexpressed in several malignancies, such as colorectal carcinoma, breast carcinoma, and cervical carcinoma [ 14 , 15 , 16 ]. As a result, transketolase could be an effective target for cancer treatment [ 13 ]. …

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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… protein associated factor 1 tricarboxylic acid TEA domain transcription factor 1 mitochondrial transcription factor A transforming growth factor‐β transforming growth factor‐β1 translocase of the inner mitochondrial membrane 23 tumor‐infiltrating myeloid cells Tat‐interacting protein of 60 kDa transketolase … Notable examples include SIRT5, which desuccinylates p53 at K120, inhibiting its transcriptional activity [ 55 ], and transketolase (TKT), activating it post‐demalonylation [ 56 ]. …

Newer laboratory methods for assessing nutriture of selected B-complex vitamins.

This review is limited to progress in the development of new or improved laboratory procedures to assess the nutriture of thiamin, riboflavin, niacin, vitamin B6, and folic acid. There has been marked progress in this area for the other vitamins as well. The increased availability of radioassay techniques and HPLC methodologies that have application in nutrition assessment is significant. However, for a number of the vitamins, there is still a need for additional methods that provide functionally interpretable preclinical information and give accurate assessment of body reserves of the nutrien

Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy.

There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule redox active compounds traditionally thought to be antioxidants. In this review we describe the potential mechanisms and clinical applicability in cancer therapy of four small molecule redox active agents: melatonin, vitamin E, selenium, and vitamin C

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… Transketolase is a critical pentose phosphate pathway mediator necessary for regenerating NADPH. Recently, transketolase has been shown to be critical in regulating cancer cell redox metabolism in hepatocellular carcinoma cells [ 13 ]. … In this model system, transketolase inhibition led to increased oxidative distress and enhanced sensitivity to sorafenib. …

The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer.

Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the c

Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).

Cisplatin resistance remains a primary obstacle in oncology, leading to therapeutic failure and disease recurrence. While resistance mechanisms are multifactorial, metabolic reprogramming has emerged as a critical adaptive strategy for cancer cells to evade cisplatin-induced cytotoxicity. This review synthesizes current evidence on how altered metabolism drives cisplatin resistance, with a particular emphasis on the pivotal role of pyruvate dehydrogenase kinases (PDKs). PDKs act as metabolic gatekeepers by inhibiting the pyruvate dehydrogenase complex (PDHC), diverting glucose flux away from m

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… Similarly, transketolase attenuates cisplatin sensitivity through GSH depletion and ROS accumulation in glioblastoma [ 85 ]. Pharmacological inhibitors of carbon metabolism have emerged as promising therapeutic strategies. …

Diseases of the Nervous System

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The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.

Supplements are widely perceived as safe and beneficial; yet in oncology, this assumption is questionable. Clinical trials over the past few decades have often produced disappointing results, raising a critical question: are these agents used correctly, or could they inadvertently cause harm? This review examines supplements frequently used in cancer care-such as oral vitamin C, berberine, N-acetylcysteine, vitamin D, vitamin E, melatonin, polyphenols, alpha-lipoic acid, selenium, and coenzyme Q10-which can act as tumor suppressors or promoters depending on dose, route, and disease stage. We e

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… This pathway can target the transketolase gene, which connects the Pentose Phosphate Pathway (PPP) with glycolysis to affect the production of the antioxidant NADPH [ 223 ]. …

Targeting mTOR and Metabolism in Cancer: Lessons and Innovations.

Cancer cells support their growth and proliferation by reprogramming their metabolism in order to gain access to nutrients. Despite the heterogeneity in genetic mutations that lead to tumorigenesis, a common alteration in tumors occurs in pathways that upregulate nutrient acquisition. A central signaling pathway that controls metabolic processes is the mTOR pathway. The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. By sen

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… Akt also phosphorylates transketolase (TKT) on Thr382, a key enzyme of the nonoxidative PPP, leading to increased flux through this pathway and increasing purine synthesis [ 159 ]. 2.7. Other Metabolic Pathways mTORC1 also promotes serine biosynthesis and one-carbon pathway metabolism. …

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

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… Additionally, increased succinylation of the K48 and K140 sites of fructose diphosphate aldolase B and of the K6 site of transketolase in the N2 stage of the pentose phosphate pathway promotes cancer cell metastasis to lymph nodes [ 56 ]. … Crotonylation at position K140 of transketolase and position K28 of aldolase C similarly inhibits their enzymatic activities via affecting the positioning of the catalytic core or intermolecular interactions [ 177 ]. …

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effe

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… nutrition, MAD: modified Atkins diet, MSCT: metabolically supported chemotherapy, OS: overall survival, PFS: progression free survival, PgR: progesterone receptor, POH: perillyl alcohol, PR: partial response, QoL: quality of life, RT: radio therapy, SD: stable disease, ST: standard therapy, TKTL1: transketolase-like …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… This includes the determination of Apo10 protein epitope (Apo10) and Transketolase-like 1 (TKTL1) in monocytes, the mRNA expression level for PD-L1 on circulating tumor cells, and the Th1/Th2 ratio [ 163 ]. …