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Dermatology (Basel, Switzerland) 2020The ultimate goal of wound healing following minor injury is to form a tissue regenerate that has functionality and visual appearance as close to the original skin as... (Review)
Review
BACKGROUND
The ultimate goal of wound healing following minor injury is to form a tissue regenerate that has functionality and visual appearance as close to the original skin as possible. The body's physiological response to any wound is traditionally characterised by three distinct steps: inflammation, proliferation and remodelling.
SUMMARY
New insights suggest that the three phases overlap (and even occur in parallel) in both time and space in the wound, necessitating a clinical approach that targets each stage simultaneously to ensure rapid repair and wound closure without further complications. Ingredients that exhibit activity across each of the three phases, such as dexpanthenol, are of value in the context of minor wound care and scar management. Key Messages: In addition to treatment and ingredient selection, it is also important to consider broader clinical best practices and self-care options that can be used to optimise the management of minor wounds. An individualised approach that can account for a patient's unique requirements and preferences is critical in achieving effective wound recovery.
Topics: Cell Movement; Cell Proliferation; Cicatrix; Dermatologic Agents; Humans; Hydrogen-Ion Concentration; Inflammation; Pantothenic Acid; Reactive Oxygen Species; Skin; Skin Physiological Phenomena; Wound Healing; Wounds and Injuries
PubMed: 31955162
DOI: 10.1159/000505291 -
Nutrients Sep 2022The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized... (Review)
Review
The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B complex intake. Most studies examined such issues concerning a specific vitamin B or life stage, with the majority reporting the effect of either excess or deficiency. Deep insight into the orchestration of the eight different B vitamins requirements is reviewed across the human life cycle, beginning from fertility and pregnancy and reaching adulthood and senility, emphasizing interactions among them and underlying action mechanisms. The effect of sex is also reviewed for each vitamin at each life stage to highlight the different daily requirements and/or outcomes. Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one's overall health in adolescence and adulthood. A higher intake of B vitamins in the elderly is also associated with preventing some aging problems, especially those related to inflammation. All supplementation should be carefully monitored to avoid toxicity and hypervitaminosis. More research should be invested in studying each vitamin individually concerning nutritional disparities in each life stage, with extensive attention paid to cultural differences and lifestyles.
Topics: Adolescent; Adult; Aged; Child; Female; Folic Acid; Humans; Male; Niacin; Pantothenic Acid; Pregnancy; Pyridoxine; Riboflavin; Sex Characteristics; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 36235591
DOI: 10.3390/nu14193940 -
Science Translational Medicine Mar 2023Patients with myelodysplastic syndrome and ring sideroblasts (MDS-RS) present with symptomatic anemia due to ineffective erythropoiesis that impedes their quality of...
Patients with myelodysplastic syndrome and ring sideroblasts (MDS-RS) present with symptomatic anemia due to ineffective erythropoiesis that impedes their quality of life and increases morbidity. More than 80% of patients with MDS-RS harbor splicing factor 3B subunit 1 (SF3B1) mutations, the founder aberration driving MDS-RS disease. Here, we report how mis-splicing of coenzyme A synthase (), induced by mutations in , affects heme biosynthesis and erythropoiesis. Our data revealed that was up-regulated during normal erythroid differentiation, and its silencing prevented the formation of erythroid colonies, impeded erythroid differentiation, and precluded heme accumulation. In patients with MDS-RS, loss of protein due to mis-splicing led to depletion of both CoA and succinyl-CoA. Supplementation with COASY substrate (vitamin B5) rescued CoA and succinyl-CoA concentrations in cells and mended erythropoiesis differentiation defects in MDS-RS primary patient cells. Our findings reveal a key role of the COASY pathway in erythroid maturation and identify upstream and downstream metabolites of COASY as a potential treatment for anemia in patients with MDS-RS.
Topics: Humans; Erythropoiesis; Pantothenic Acid; Quality of Life; Anemia; Transcription Factors; Myelodysplastic Syndromes; Heme; RNA Splicing Factors; Phosphoproteins
PubMed: 36857430
DOI: 10.1126/scitranslmed.abn5135 -
Nature Aug 2022In response to hormones and growth factors, the class I phosphoinositide-3-kinase (PI3K) signalling network functions as a major regulator of metabolism and growth,...
In response to hormones and growth factors, the class I phosphoinositide-3-kinase (PI3K) signalling network functions as a major regulator of metabolism and growth, governing cellular nutrient uptake, energy generation, reducing cofactor production and macromolecule biosynthesis. Many of the driver mutations in cancer with the highest recurrence, including in receptor tyrosine kinases, Ras, PTEN and PI3K, pathologically activate PI3K signalling. However, our understanding of the core metabolic program controlled by PI3K is almost certainly incomplete. Here, using mass-spectrometry-based metabolomics and isotope tracing, we show that PI3K signalling stimulates the de novo synthesis of one of the most pivotal metabolic cofactors: coenzyme A (CoA). CoA is the major carrier of activated acyl groups in cells and is synthesized from cysteine, ATP and the essential nutrient vitamin B5 (also known as pantothenate). We identify pantothenate kinase 2 (PANK2) and PANK4 as substrates of the PI3K effector kinase AKT. Although PANK2 is known to catalyse the rate-determining first step of CoA synthesis, we find that the minimally characterized but highly conserved PANK4 is a rate-limiting suppressor of CoA synthesis through its metabolite phosphatase activity. Phosphorylation of PANK4 by AKT relieves this suppression. Ultimately, the PI3K-PANK4 axis regulates the abundance of acetyl-CoA and other acyl-CoAs, CoA-dependent processes such as lipid metabolism and proliferation. We propose that these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone/growth-factor-driven or oncogene-driven metabolism and growth.
Topics: Acetyl Coenzyme A; Adenosine Triphosphate; Cell Proliferation; Coenzyme A; Cysteine; Lipid Metabolism; Mass Spectrometry; Metabolomics; Pantothenic Acid; Phosphatidylinositol 3-Kinase; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 35896750
DOI: 10.1038/s41586-022-04984-8 -
Shokuhin Eiseigaku Zasshi. Journal of... 2023A simple and reliable analytical method has been developed for the determination of pantothenic acid in food. For the high-protein food, 20 mL of water was added to 2 g...
A simple and reliable analytical method has been developed for the determination of pantothenic acid in food. For the high-protein food, 20 mL of water was added to 2 g of sample, and after homogenization extraction, 1 mL of 15% zinc sulfate solution was added, mixed well, centrifuged, and the supernatant was filtered to make the test solution. For the low-protein food, 20 mL of 1% formic acid solution was added to 2 g of sample, homogenized, extracted, centrifuged, and the supernatant was filtered to make the test solution. The HPLC separation was carried out on a L-column2 ODS column with 0.02 mol/L phosphate solution (pH 3.0)- acetonitrile (95 : 5) as the mobile phase, and detected at 200 nm. The LC-MS/MS conditions were L-column2 ODS as the separation column, 5 mmol/L ammonium formate (containing 0.01% formic acid)-methanol (85 : 15) as the mobile phase, and multiple reaction monitoring (MRM) was used for detection. The recoveries of pantothenic acid in milk powder and nutritional food products were more than 88% with high precision. As a result of analyzing commetrcially available foods labeled as containing pantothenic acid, analytical values almost identical to the labeled values were obtained, and a high correlation was observed between the values obtained by HPLC and LC-MS/MS.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Pantothenic Acid; Tandem Mass Spectrometry
PubMed: 36858591
DOI: 10.3358/shokueishi.64.47 -
Current Issues in Molecular Biology Sep 2021Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been...
Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; β-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-β1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.
Topics: Antigens, Surface; Apoptosis; Biomarkers; Cell Proliferation; Cells, Cultured; Cellular Senescence; Gene Expression; Gene Expression Regulation; Hair Follicle; Humans; Pantothenic Acid; RNA, Messenger; Vitamin B Complex
PubMed: 34698060
DOI: 10.3390/cimb43030097 -
Veterinary Pathology Jan 2023This report describes 2 events of degenerative myelopathy in 4- to 27-day-old piglets, with mortality rates reaching 40%. Sows were fed rations containing low levels of...
This report describes 2 events of degenerative myelopathy in 4- to 27-day-old piglets, with mortality rates reaching 40%. Sows were fed rations containing low levels of pantothenic acid. Piglets presented with severe depression, weakness, ataxia, and paresis, which were more pronounced in the pelvic limbs. No significant gross lesions were observed. Histologically, there were degeneration and necrosis of neurons in the spinal cord, primarily in the thoracic nucleus in the thoracic and lumbar segments, and motor neurons in nucleus IX of the ventral horn in the cervical and lumbar intumescence. Minimal-to-moderate axonal and myelin degeneration was observed in the dorsal funiculus of the spinal cord and in the dorsal and ventral nerve roots. Immunohistochemistry demonstrated depletion of acetylcholine neurotransmitters in motor neurons and accumulation of neurofilaments in the perikaryon of neurons in the thoracic nucleus and motor neurons. Ultrastructurally, the thoracic nucleus neurons and motor neurons showed dissolution of Nissl granulation. The topographical distribution of the lesions indicates damage to the second-order neurons of the spinocerebellar tract, first-order axon cuneocerebellar tract, and dorsal column-medial lemniscus pathway as the cause of the conscious and unconscious proprioceptive deficit, and damage to the alpha motor neuron as the cause of the motor deficit. Clinical signs reversed and no new cases occurred after pantothenic acid levels were corrected in the ration, and piglets received parenteral administration of pantothenic acid. This study highlights the important and practical use of detailed neuropathological analysis to refine differential diagnosis.
Topics: Animals; Swine; Female; Pantothenic Acid; Spinal Cord; Neurons; Medulla Oblongata; Spinal Cord Diseases; Swine Diseases
PubMed: 36250539
DOI: 10.1177/03009858221128920 -
Nature Communications Apr 2022Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class...
Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a > 30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission.
Topics: Animals; Antimalarials; Folic Acid Antagonists; Malaria; Malaria, Falciparum; Malaria, Vivax; Mice; Pantothenic Acid; Plasmodium falciparum; Rats
PubMed: 35444200
DOI: 10.1038/s41467-022-29688-5 -
British Medical Journal Mar 1952
Topics: Humans; Pantothenic Acid
PubMed: 14905015
DOI: No ID Found -
Oncoimmunology 2022Vitamin B5 (panthotenic acid), the precursor of coenzyme A (CoA), is contained in most food items and is produced by the intestinal microbiota. A recent study published...
Vitamin B5 (panthotenic acid), the precursor of coenzyme A (CoA), is contained in most food items and is produced by the intestinal microbiota. A recent study published in reports that vitamin B5 and CoA favor the differentiation of CD8 cytotoxic T cells into interleukin-22 (IL-22)-producing Tc22 cells, likely through fueling mitochondrial metabolism. Importantly, in a small cohort of melanoma patients, the plasma levels of vitamin B5 positively correlate with responses to PD-1-targeted immunotherapy. Moreover, in mice, supplementation with vitamin B5 increases the efficacy of PD-L1-targeted cancer immunotherapy, and culture of T cells with CoA enhances their antitumor activity upon adoptive transfer into mice. These finding suggest that vitamin B5 is yet another B vitamin that stimulates anti-cancer immunosurveillance.
Topics: Animals; Coenzyme A; Gastrointestinal Microbiome; Humans; Immunologic Factors; Immunotherapy; Melanoma; Mice; Pantothenic Acid
PubMed: 35096488
DOI: 10.1080/2162402X.2022.2031500