RESUMO
Brown fat is a therapeutic target for the treatment of obesity-associated metabolic diseases. However, nutritional intervention strategies for increasing the mass and activity of human brown adipocytes have not yet been established. To identify vitamins required for brown adipogenesis and adipocyte browning, chemical compound-induced brown adipocytes (ciBAs) were converted from human dermal fibroblasts under serum-free and vitamin-free conditions. Choline was found to be essential for adipogenesis. Additional treatment with pantothenic acid (PA) provided choline-induced immature adipocytes with browning properties and metabolic maturation, including uncoupling protein 1 (UCP1) expression, lipolysis, and mitochondrial respiration. However, treatment with high PA concentrations attenuated these effects along with decreased glycolysis. Transcriptome analysis showed that a low PA concentration activated metabolic genes, including the futile creatine cycle-related thermogenic genes, which was reversed by a high PA concentration. Riboflavin treatment suppressed thermogenic gene expression and increased lipolysis, implying a metabolic pathway different from that of PA. Thiamine treatment slightly activated thermogenic genes along with decreased glycolysis. In summary, our results suggest that specific B vitamins and choline are uniquely involved in the regulation of adipocyte browning via cellular energy metabolism in a concentration-dependent manner.
Assuntos
Adipócitos Marrons , Colina , Ácido Pantotênico , Riboflavina , Tiamina , Humanos , Riboflavina/farmacologia , Ácido Pantotênico/farmacologia , Ácido Pantotênico/metabolismo , Adipócitos Marrons/metabolismo , Adipócitos Marrons/efeitos dos fármacos , Tiamina/farmacologia , Tiamina/metabolismo , Colina/metabolismo , Colina/farmacologia , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Lipólise/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Células Cultivadas , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacosRESUMO
Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.
Assuntos
Proliferação de Células , Dano ao DNA , Neoplasias Ovarianas , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Humanos , Dano ao DNA/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Proliferação de Células/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Piridoxina/farmacologia , Camundongos , Ácido Fólico/farmacologia , Ácido Fólico/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto , Suplementos Nutricionais , Antineoplásicos/farmacologia , Administração Oral , Vitamina B 6/farmacologia , Vitamina B 6/administração & dosagem , Histonas/metabolismo , Sulfato de Zinco , Vitamina B 12 , Extratos Vegetais , Ácido Pantotênico , Ácido AscórbicoRESUMO
Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies.
Assuntos
Antifúngicos , Mitocôndrias , Saccharomyces cerevisiae , Vacúolos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Vacúolos/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Ácido Pantotênico/metabolismo , Farmacorresistência Fúngica/genética , Inativação MetabólicaRESUMO
The CRISPR-based regulation tools enable fine-tuning of gene transcription, showing potential in areas of biomanufacturing and live therapeutics. However, the cell toxicity and PAM specificity of existing CRISPR-based regulation systems limit their broad application. The development of new and less-toxic CRISPR-controlled expression systems remains highly desirable for expanding the application scope of CRISPR-based tools. Here, we reconstituted the type I CRISPR-Cas system from Escherichia coli to finely tune gene expression in Bacillus subtilis. Through engineering the 5' untranslated region (UTR) of mRNAs of cas genes, we remarkably improved the efficacy of the type I CRISPRi system. The improved type I CRISPRi system was applied in engineering the D-pantothenic acid (DPA)-producing B. subtilis, which was generated by strengthening the metabolic flux toward ß-alanine and (R)-pantoate via enhancing expression of key enzymes at both transcriptional and translational levels. Through controlling the expression of pdhA with the CRISPRi system for fine-tuning the metabolic flux toward DPA and the TCA cycle, we elevated the DPA titer to 0.88 g/L in shake flasks and 12.81 g/L in fed-batch fermentations without the addition of the precursor ß-alanine. The type I CRISPRi system and the strategy for fine-tuning metabolic flux reported here not only enrich the CRISPR toolbox in B. subtilis and facilitate DPA production through microbial fermentation but also provide a paradigm for programming important organisms to produce value-added chemicals with cheap raw materials.
Assuntos
Bacillus subtilis , Sistemas CRISPR-Cas , Escherichia coli , Engenharia Metabólica , Ácido Pantotênico , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Sistemas CRISPR-Cas/genética , Engenharia Metabólica/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Pantotênico/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Regiões 5' não Traduzidas/genética , Regulação Bacteriana da Expressão GênicaRESUMO
Vitamin B5 [D-pantothenic acid (D-PA)] is an essential water-soluble vitamin that is widely used in the food and feed industries. Currently, the relatively low fermentation efficiency limits the industrial application of D-PA. Here, a plasmid-free D-PA hyperproducer was constructed using systematic metabolic engineering strategies. First, pyruvate was enriched by deleting the non-phosphotransferase system, inhibiting pyruvate competitive branches, and dynamically controlling the TCA cycle. Next, the (R)-pantoate pathway was enhanced by screening the rate-limiting enzyme PanBC and regulating the other enzymes of this pathway one by one. Then, to enhance NADPH sustainability, NADPH regeneration was achieved through the novel "PEACES" system by (1) expressing the NAD + kinase gene ppnk from Clostridium glutamicum and the NADP + -dependent gapCcae from Clostridium acetobutyricum and (2) knocking-out the endogenous sthA gene, which interacts with ilvC and panE in the D-PA biosynthesis pathway. Combined with transcriptome analysis, it was found that the membrane proteins OmpC and TolR promoted D-PA efflux by increasing membrane fluidity. Strain PA132 produced a D-PA titer of 83.26 g/L by two-stage fed-batch fermentation, which is the highest D-PA titer reported so far. This work established competitive producers for the industrial production of D-PA and provided an effective strategy for the production of related products.
Assuntos
Escherichia coli , Engenharia Metabólica , Ácido Pantotênico , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Pantotênico/biossíntese , Ácido Pantotênico/metabolismoRESUMO
OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 â for 30 min, then incubated with papain and acid phosphatase at 45 â for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.
Assuntos
Leite , Espectrometria de Massas em Tandem , Leite/química , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Niacinamida/análise , Riboflavina/análise , Nutrientes/análise , Ácido Pantotênico/análise , Bovinos , Piridoxina/análise , Niacina/análise , Carnitina/análiseRESUMO
Background: Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell metabolism, synthesis of nucleotides, and neurotransmitters, the present study systematically investigated the plasma levels of vitamins B9 and B12 in children with ADHD. Methods: We searched electronic databases including Web of Science, MEDLINE, EMBASE, Scopus, Iran MEDEX, Cochran database, and SID from conception to June 2023. Full-text case-control or cross-sectional studies were included in this study. Participants in the case group were children with ADHD aged 6-12 years. Review Manager Software (RevMan 5.4) was used for statistical analyses. Standardized mean differences (SMD) with 95% CIs were used to determine the differences between the two groups. Results: Six studies were included in the present meta-analysis. They included 982 children, of whom, 204 were girls and 744 were boys. The mean age of the children was 8.86±2.03 years. The level of vitamin B9 was significantly different between children with and without ADHD [SMD -0.80, 95% CI (-1.55, -0.04)]. Vitamin B12 was significantly lower in children with ADHD [SMD -0.29, 95% CI (-0.42, -0.16)]. However, due to high heterogeneity (I2 = 93%), sensitivity analysis was used, I2 fell to 21%, and significant difference was observed between the two groups [SMD -0.19, 95% CI (-0.34, -0.04)]. Conclusion: The results of this systematic review showed that the level of vitamins B9 and B12 in children with ADHD was significantly lower than that in healthy children.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Vitamina B 12 , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Vitamina B 12/sangue , Criança , Feminino , Masculino , Ácido Pantotênico/sangue , Estudos Transversais , Estudos de Casos e ControlesRESUMO
OBJECTIVE: To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of this pathology. MATERIAL AND METHODS: A total of 90 children aged 8 to 10 years were examined. Of these, the main study group consisted of 30 children with NCT, the comparison group consisted of 30 children with a combined type of attention deficit hyperactivity disorder ADHD (ADHD-K), the control group consisted of 30 children without neuropsychiatric disorders. The study used clinical, neurophysiological (electroencephalography (EEG)) and parametric methods. The CMAS scale of apparent anxiety (The Children's Form of Manifest Anxiety Scale), the SNAP-IY scale (assessment of the degree of inattention, hyperactivity and impulsivity), the TOVA computer test (the Test of Variables of Attention), the scale «SCT¼ (Sluggish Cognitive Tempo) for assessing manifestations of low cognitive tempo, the «RAM¼ technique for quantifying working memory. Pantogam was used to treat patients at a dose of 750 mg per day for 8 weeks. RESULTS: Patients with NCT are characterized by more pronounced attention disorders compared with healthy peers and with children with ADHD-K, and they have a decrease in mainly not selective attention, but the overall level of functional activity. Also, the group of children with NCT has an increased level of anxiety compared to the group of children with ADHD. A comparative analysis of the level of impulsivity showed that children with NCT are less characterized by a deficit in inhibition processes. According to the quantitative analysis of the EEG, specific changes in functional activity in the frontal and central regions of the cerebral cortex were revealed (a statistically significant increase in the ratio of absolute theta rhythm to beta1 rhythm, compared with other groups), reflecting insufficient cortical arousal and less focused neural states. When re-evaluating the condition of children with NCT after a course of therapy with Pantogam, an improvement in the form of a decrease in the degree of inattention, the severity of memory impairment and a decrease in reaction time was recorded in 60% of cases. According to quantitative EEG analysis, there was a significant decrease in the ratio of absolute theta rhythm to beta1 rhythm in the central leads of both hemispheres and in the parietal-temporal leads of the left hemisphere, indicating an increase in the level of overall activation of the cerebral cortex after a course of treatment. CONCLUSION: Clinical and neurophysiological differences were revealed in patients with NCT and with combined ADHD. It has been shown that the use of Pantogam for the treatment of children with NCT leads not only to a decrease in the main manifestations of this disorder, but also to an improvement in the functional state of the brain.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Eletroencefalografia , Ácido Pantotênico , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Masculino , Feminino , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/uso terapêutico , Cognição , Atenção/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Ácido gama-Aminobutírico/análogos & derivadosRESUMO
Background: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be. Objective: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains. Methods: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) across ten brain regions. Case-control differences were determined by nonparametric Mann-Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD. Results: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum. Conclusions: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.
Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer's disease, Parkinson's disease dementia, and Huntington's disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatographymass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampuslooking most similar to the pattern of changes already seen in Alzheimer's disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms.
Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Ácido Pantotênico , Humanos , Idoso , Masculino , Doença por Corpos de Lewy/metabolismo , Feminino , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Estudos de Casos e Controles , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta PressãoRESUMO
Plants used in traditional medicine offer an affordable new alternative in tissue repair therapy. This study aimed to evaluate the effectiveness of the 5% Rhizophora mangle cream compared to the 5% dexpanthenol cream in healing open surgical wounds on the upper eyelid. A total of 18 patients were submitted to the experiment and divided into 2 groups with 9 patients each who used topically and daily 5% dexpanthenol cream (control group) or 5% R.mangle cream (intervention group) for 7 days. Clinical, morphometric and histomorphometric analyses of wounds and surgical procedures for skin removal were performed. In the morphometric analysis, all wounds treated with R.mangle and dexpanthenol creams showed complete macroscopic scars, without inflammatory signs and infection free. The skin hydration values in pre and post application periods of the cream were 43.82 ± 43.93 and 62.12 ± 67.40 respectively. The histomorphometric study showed lower values of epithelium distance in R. mangle group and higher in dexpanthenol group with significant difference between groups (p < 0.05). The R.mangle 5% cream proved to be effective in healing wounds of human upper eyelid skin with a significant improvement in epithelization compared to dexpanthenol 5% cream.
Assuntos
Ácido Pantotênico/análogos & derivados , Rhizophoraceae , Cicatrização , Humanos , Brasil , Pálpebras/cirurgiaRESUMO
This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.
Assuntos
Ceco , Ácido Pantotênico , Animais , Ácido Butírico , Diferenciação Celular , Suplementos Nutricionais , SuínosRESUMO
In dry skin (DS), skin-barrier function is easily disturbed and moisturizing factors in the stratum corneum are reduced. Despite being a common condition, DS is often overlooked in patients with advanced age or comorbid diseases. In September 2022, specialists in dermatology and skin care met to discuss unmet needs and management of patients with DS with existing medical conditions or DS induced by ongoing pharmacological treatments. There was consensus about the need to improve the current understanding and management of DS in patients with comorbidities, including type 2 diabetes, chronic kidney disease, radiodermatitis, and photodamaged skin. Clinical guidance related to optimal treatment of DS in patients with advanced age or comorbid diseases is needed. Dexpanthenol-containing emollients have been shown to provide rapid relief from the symptoms and clinical signs of skin inflammation and are well-tolerated and effective in terms of moisturizing and soothing DS and maintaining skin-barrier function. Thus, dexpanthenol-containing emollients may play an important role in future management of DS. Further research is needed to elucidate the efficacy of dexpanthenol across the spectrum of DS, irrespective of comorbidity status or age.
Assuntos
Diabetes Mellitus Tipo 2 , Ictiose , Ácido Pantotênico/análogos & derivados , Humanos , Emolientes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ictiose/tratamento farmacológico , Veículos Farmacêuticos , ComorbidadeRESUMO
Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2'-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption. Here, we investigated how 2'-FL prevents colitis in adulthood through its effects on the gut microbial community. We found that the gut microbiota from adult mice that consumed 2'-FL exhibited an increase in abundance of several health-associated genera, including Bifidobacterium and Lactobacillus. The 2'-FL-modulated gut microbial community exerted preventive effects on colitis in adult mice. By using Bifidobacterium infantis as a 2'-FL-consuming bacterial model, exploratory metabolomics revealed novel 2'-FL-enriched secretory metabolites by Bifidobacterium infantis, including pantothenol. Importantly, pantothenate significantly protected the intestinal barrier against oxidative stress and mitigated colitis in adult mice. Furthermore, microbial metabolic pathway analysis identified 26 dysregulated metabolic pathways in fecal microbiota from patients with ulcerative colitis, which were significantly regulated by 2'-FL treatment in adult mice, indicating that 2'-FL has the potential to rectify dysregulated microbial metabolism in colitis. These findings support the contribution of the 2'-FL-shaped gut microbial community and bacterial metabolite production to the protection of intestinal integrity and prevention of intestinal inflammation in adulthood.IMPORTANCEAt present, neither basic research nor clinical studies have revealed the exact biological functions or mechanisms of action of individual oligosaccharides during development or in adulthood. Thus, it remains largely unknown whether human milk oligosaccharides could serve as effective therapeutics for gastrointestinal-related diseases. Results from the present study uncover 2'-FL-driven alterations in bacterial metabolism and identify novel B. infantis-secreted metabolites following the consumption of 2'-FL, including pantothenol. This work further demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice. Remarkably, 2'-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients. These novel metabolic pathways underlying the bioactivities of 2'-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis.
Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Ácido Pantotênico/análogos & derivados , Adulto , Humanos , Animais , Camundongos , Leite Humano , Colite Ulcerativa/metabolismo , Oligossacarídeos/metabolismo , Colite/prevenção & controle , InflamaçãoRESUMO
RESEARCH QUESTION: Does dexpanthenol work as an effective therapeutic agent against cyclophosphamide (CYC)-induced premature ovarian failure (POF) in rats? DESIGN: A total of 28 female Wistar Albino rats were randomly divided into four groups (nâ¯=â¯7 per group). The POF and POF plus dexpanthenol groups were intraperitoneally administered CYC at an initial dose of 50 mg/kg, followed by 8 mg/kg for 14 days. The dexpanthenol and POF plus dexpanthenol groups were both intraperitoneally administered dexpanthenol at a dose of 500 mg/kg/day for 15 days. RESULTS: In the group administered CYC, the following was observed: a decrease in the ovarian index; a decrease in the numbers of primordial, primary, secondary and antral follicles; an increase in the number of corpus luteum and atretic follicles; a decrease in proliferation cell nuclear antigen immunoreactivity; a significant reduction in anti-Müllerian hormone and oestradiol levels; and an increase in serum FSH levels compared with controls. Dexpanthenol, on the other hand, reversed these effects. Quantitative reverse transcription polymerase chain reaction analyses showed that dexpanthenol increased Bcl-2, Akt1, mTOR, Nrf2 and HO-1 in CYC-induced ovarian tissues, but decreased Bax, Cas3, Hsp27, Hsp70, and Hsp90. Dexpanthenol treatment has a potential for inhibiting the intrinsic apoptotic pathway and oxidative stress levels in ovarian tissues via the downregulation of the mRNA expression of heat shock proteins and the activation of Nrf2/HO-1 pathways. CONCLUSIONS: Our findings demonstrated that dexpanthenol is an effective agent against POF caused by CYC; however, further experimental and clinical data are needed to use it effectively.
Assuntos
Ciclofosfamida , Ovário , Ácido Pantotênico , Insuficiência Ovariana Primária , Ratos Wistar , Animais , Feminino , Ciclofosfamida/toxicidade , Ciclofosfamida/efeitos adversos , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/farmacologia , Ovário/efeitos dos fármacos , Ovário/patologia , Insuficiência Ovariana Primária/induzido quimicamente , Ratos , Folículo Ovariano/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Hormônio Foliculoestimulante/sangue , Serina-Treonina Quinases TOR/metabolismo , Hormônio Antimülleriano/sangueRESUMO
BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.
Assuntos
Biotina , Ácido Pantotênico , Valeratos , Feminino , Humanos , Lactente , Biotina/uso terapêutico , Vitaminas , Suplementos Nutricionais , SódioRESUMO
BACKGROUND: The protection for different skin types with impaired skin barrier in the market is insufficient. AIM: To evaluate the efficacy and safety of a panthenol-enriched mask (La Roche-Posay Mask Pro) in addressing various skin barrier impairment subgroups, including dry sensitive, oily sensitive, and oily acne skin. METHODS: A total of 177 participants were enrolled in the study and divided into three subgroups based on their skin type. Participants used the mask following the specified protocol, with measurements taken for skin hydration, transepidermal water loss (TEWL), sebum content, and skin redness-factors that are directly influenced by skin barrier function. Assessments were conducted at baseline and after 1 day (tested 15 min post-application), 7 days, and 14 days of application using Sebumeter, Tewameter, Corneometer, Mexameter, and VISIA. RESULTS: Results showed significant improvements in skin parameters across all subgroups. In the dry sensitive skin subgroup, the mask increased skin hydration, sebum content, and reduced redness. For the oily sensitive skin subgroup, the mask regulated sebum production and improved skin hydration. In the oily acne skin subgroup, the mask reduced sebum content, redness, TEWL, and post-inflammatory erythema and hyperpigmentation. Tolerance was excellent for all skin types, with no adverse reactions observed. CONCLUSIONS: This study highlights the efficacy and safety of the panthenol-enriched LRP Mask Pro for individuals with distinct skin barrier impairment subgroups. The mask's versatile formulation and proven efficacy make it a valuable skincare product for addressing various skin concerns and achieving healthier, more balanced skin.
Assuntos
Acne Vulgar , Ácido Pantotênico , Perda Insensível de Água , Humanos , Feminino , Adulto , Ácido Pantotênico/administração & dosagem , Ácido Pantotênico/efeitos adversos , Ácido Pantotênico/análogos & derivados , Masculino , Adulto Jovem , Perda Insensível de Água/efeitos dos fármacos , Acne Vulgar/tratamento farmacológico , Sebo/metabolismo , Sebo/efeitos dos fármacos , Pessoa de Meia-Idade , Resultado do Tratamento , Pele/efeitos dos fármacos , Adolescente , Administração Cutânea , Eritema/etiologia , Eritema/induzido quimicamenteRESUMO
Salt stress negatively affects rice growth, development and yield. Metabolic adjustments contribute to the adaptation of rice under salt stress. Branched-chain amino acids (BCAA) are three essential amino acids that cannot be synthesized by humans or animals. However, little is known about the role of BCAA in response to salt stress in plants. Here, we showed that BCAAs may function as scavengers of reactive oxygen species (ROS) to provide protection against damage caused by salinity. We determined that branched-chain aminotransferase 2 (OsBCAT2), a protein responsible for the degradation of BCAA, positively regulates salt tolerance. Salt significantly induces the expression of OsBCAT2 rather than BCAA synthesis genes, which indicated that salt mainly promotes BCAA degradation and not de novo synthesis. Metabolomics analysis revealed that vitamin B5 (VB5) biosynthesis pathway intermediates were higher in the OsBCAT2-overexpressing plants but lower in osbcat2 mutants under salt stress. The salt stress-sensitive phenotypes of the osbcat2 mutants are rescued by exogenous VB5, indicating that OsBCAT2 affects rice salt tolerance by regulating VB5 synthesis. Our work provides new insights into the enzymes involved in BCAAs degradation and VB5 biosynthesis and sheds light on the molecular mechanism of BCAAs in response to salt stress.
Assuntos
Aminoácidos de Cadeia Ramificada , Ácido Pantotênico , Humanos , Animais , Aminoácidos de Cadeia Ramificada/metabolismo , Tolerância ao Sal/genética , MetabolômicaRESUMO
Chronic tobacco use can lead to liver damage and inflammation due to the accumulation of various toxins in the body. This study aimed to investigate the correlation between the molecular mechanisms of nicotine-induced liver injury, the caspase cascade, and the Akt/NF-κB signaling pathway, as well as the protective effects of dexpanthenol (DEX). Male rats were subjected to intraperitoneal injections of nicotine at a concentration of 0.5 mg/kg/day and/or DEX at a concentration of 500 mg/kg/day for 8 weeks. After the treatment period, liver function tests were conducted on serum samples, and tissue samples were analyzed for protein levels of Akt, NF-κB, Bax, Bcl-xL, Caspase-3, and Caspase-9, along with histopathological changes. Additionally, assessments of oxidative stress markers and proinflammatory cytokines were carried out. Nicotine administration led to elevated levels of IL-6, IL-1ß, MDA, TOS, and oxidative stress index, accompanied by decreased TAS levels. Moreover, nicotine exposure reduced the p-Akt/Akt ratio, increased NF-κB, Bax, Caspase-3, and Caspase-9 protein levels, and decreased the antiapoptotic protein Bcl-xL levels. DEX treatment significantly mitigated these effects, restoring the parameters to levels comparable to those of the control group. Nicotine-induced liver injury resulted in oxidative stress, inflammation, and apoptosis, mediated by Bax/Bcl-xL, Caspase-3, Caspase-9, and Akt/NF-κB pathways. Conversely, DEX effectively attenuated nicotine-induced liver injury by modulating apoptosis through NF-κB, Caspase-3, Caspase-9, Bax inhibition, and Bcl-xL activation.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Nicotina , Ácido Pantotênico , Animais , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Apoptose , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Nicotina/efeitos adversos , Estresse Oxidativo , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management. AIM: To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin. METHODS: A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants. RESULTS: After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants. CONCLUSION: The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.
Assuntos
Dermatoses Faciais , Probióticos , Humanos , Prebióticos/efeitos adversos , Probióticos/efeitos adversos , Ácido Pantotênico , EmolientesRESUMO
Pantothetic acid is required for metabolic activity that supports MYC-driven breast tumor growth.