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Journal of Mammary Gland Biology and... Feb 2023The production of antimicrobial components and the formation of less-permeable tight junctions (TJs) are important in the defense system of lactating mammary glands and...
The production of antimicrobial components and the formation of less-permeable tight junctions (TJs) are important in the defense system of lactating mammary glands and for safe dairy production. Valine is a branched-chain amino acid that is actively consumed in the mammary glands and promotes the production of major milk components like β-casein; additionally, branched-chain amino acids stimulate antimicrobial component production in the intestines. Therefore, we hypothesized that valine strengthens the mammary gland defense system without influencing milk production. We investigated the effects of valine in vitro using cultured mammary epithelial cells (MECs) and in vivo using the mammary glands of lactating Tokara goats. Valine treatment at 4 mM increased the secretion of S100A7 and lactoferrin as well as the intracellular concentration of β-defensin 1 and cathelicidin 7 in cultured MECs. In addition, an intravenous injection of valine increased S100A7 levels in the milk of Tokara goats without influencing milk yield and milk components (i.e., fat, protein, lactose, and solids). In contrast, valine treatment did not affect TJ barrier function either in vitro or in vivo. These findings indicate that valine enhances antimicrobial component production without influencing milk production and TJ barrier function in lactating mammary glands; thus, valine contributes to safe dairy production.
Topics: Female; Animals; Milk; Tight Junctions; Lactation; Valine; Mammary Glands, Animal; Epithelial Cells; Anti-Infective Agents; Goats
PubMed: 36801983
DOI: 10.1007/s10911-023-09529-x -
Profiles of Drug Substances,... 2015Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. Generally, valsartan is available as film-coated tablets. This review... (Review)
Review
Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. Generally, valsartan is available as film-coated tablets. This review summarizes thermal analysis, spectroscopy characteristics (UV, IR, MS, and NMR), polymorphism forms, impurities, and related compounds of valsartan. The methods of analysis of valsartan in pharmaceutical dosage forms and in biological fluids using spectrophotometer, CE, TLC, and HPLC methods are discussed in details. Both official and nonofficial methods are described. It is recommended to use LC-MS method for analyzing valsartan in complex matrices such as biological fluids and herbal preparations; in this case, MRM is preferred than SIM method.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Chemistry, Pharmaceutical; Humans; Molecular Structure; Technology, Pharmaceutical; Tetrazoles; Valine; Valsartan
PubMed: 26051690
DOI: 10.1016/bs.podrm.2015.01.004 -
Oxidative Medicine and Cellular... 2021Valine is an important essential amino acid of laying hens. Dietary supplemented with BCAAs ameliorated gut microbiota, whereas elevated blood levels of BCAAs are...
Valine is an important essential amino acid of laying hens. Dietary supplemented with BCAAs ameliorated gut microbiota, whereas elevated blood levels of BCAAs are positively associated with obesity, insulin resistance, and diabetes in both humans and rodents. General controlled nonrepressed (GCN2) kinase plays a crucial role in regulating intestinal inflammation and hepatic fatty acid homeostasis during amino acids deficiency, while GCN2 deficient results in enhanced intestinal inflammation and developed hepatic steatosis. However, how long-term dietary valine impacts gut health and the development of nonalcoholic fatty liver disease (NAFLD) remains unknown. Hence, in the present study, we elucidated the effects of dietary valine on intestinal barrier function, microbial homeostasis, and the development of NAFLD. A total of 960 healthy 33-weeks-old laying hens were randomly divided into five experimental groups and fed with valine at the following different levels in a feeding trial that lasted 8 weeks: 0.59, 0.64, 0.69, 0.74, and 0.79%, respectively. After 8 weeks of treatment, related tissues and cecal contents were obtained for further analysis. The results showed that diet supplemented with valine ameliorated gut health by improving intestinal villus morphology, enhancing intestinal barrier, decreasing cecum pathogenic bacteria abundances such as and , and inhibiting inflammatory response mediated by GCN2. However, long-term intake of high levels of dietary valine (0.74 and 0.79%) accelerated the development of NAFLD of laying hens by promoting lipogenesis and inhibiting fatty acid oxidation mediated by GCN2-eIF2-ATF4. Furthermore, NAFLD induced by high levels of dietary valine (0.74 and 0.79%) resulted in strengthening oxidative stress, ER stress, and inflammatory response. Our results revealed that high levels of valine are a key regulator of gut health and the adverse metabolic response to NAFLD and suggested reducing dietary valine as a new approach to preventing NAFLD of laying hens.
Topics: Animals; Chickens; Female; Humans; Mice; Non-alcoholic Fatty Liver Disease; Valine
PubMed: 34484560
DOI: 10.1155/2021/4704771 -
Nutrition Reviews Sep 1957
Topics: Humans; Valine
PubMed: 13465080
DOI: 10.1111/j.1753-4887.1957.tb00599.x -
Theriogenology Feb 2024The branched-chain amino acids (BCAAs: leucine, isoleucine and valine) are essential for animal growth and metabolic health. However, the effect of valine on male...
The branched-chain amino acids (BCAAs: leucine, isoleucine and valine) are essential for animal growth and metabolic health. However, the effect of valine on male reproduction and its underlying molecular mechanism remain largely unknown. Here, we showed that l-valine supplementation (0.30% or 0.45%, water drinking for 3 weeks) did not change body and testis weights, but significantly altered morphology of sertoli cells and germ cells within seminiferous tubule, and enlarged the space between seminiferous tubules within mouse testis. l-valine treatment (0.45%) increased significantly the Caspase3/9 mRNA levels and CASPASE9 protein levels, therefore induced apoptosis of mouse testis. Moreover, gene expression levels related to autophagy (Atg5 and Lamb3), DNA 5 mC methylation (Dnmt1, Dnmt3a, Tet2 and Tet3), RNA m6A methylation (Mettl14, Alkbh5 and Fto), and m6A methylation binding proteins (Ythdf1/2/3 and Igf2bp1/2) were significantly reduced. Protein abundances of ALKBH5, FTO and YTHDF3 were also significantly reduced, but not for ATG5 and TET2. Testis transcriptome sequencing detected 537 differentially expressed genes (DEGs, 26 up-regulated and 511 down-regulated), involved in multiple important signaling pathways. RT-qPCR validated 8 of 9 DEGs (Cd36, Scd1, Insl3, Anxa5, Lcn2, Hsd17b3, Cyp11a1, Cyp17a1 and Agt) to be decreased significantly, consistent with RNA-seq results. Taken together, l-valine treatment could disturb multiple signaling pathways (autophagy and RNA methylation etc.), and induce apoptosis to destroy the tissue structure of mouse testis.
Topics: Mice; Male; Animals; Testis; Valine; Sertoli Cells; Apoptosis; Dietary Supplements
PubMed: 38000127
DOI: 10.1016/j.theriogenology.2023.11.020 -
Bioorganic & Medicinal Chemistry Jul 2023To develop matrix metalloproteinase inhibitors (MMPIs) for both therapy and medicinal imaging by fluorescence-based techniques or positron-emission tomography (PET), a...
To develop matrix metalloproteinase inhibitors (MMPIs) for both therapy and medicinal imaging by fluorescence-based techniques or positron-emission tomography (PET), a small library of eighteen N-substituted N-arylsulfonamido d-valines were synthesized and their potency to inhibit two gelatinases (MMP-2, and MMP-9), two collagenases (MMP-8, and MMP-13) and macrophage elastase (MMP-12) was determined in a Structure-Activity-Relation study with ({4-[3-(5-methylthiophen-2-yl)-1,2,4-oxadiazol-5-yl]phenyl}sulfonyl)-d-valine (1) as a lead. All compounds were shown to be more potent MMP-2/-9 inhibitors (nanomolar range) compared to other tested MMPs. This is a remarkable result considering that a carboxylic acid group is the zinc binding moiety. The compound with a terminal fluoropropyltriazole group at the furan ring (P1' substituent) was only four times less potent in inhibiting MMP-2 activity than the lead compound 1, making this compound a promising probe for PET application (after using a prosthetic group approach to introduce fluorine-18). Compounds with a TEG spacer and a terminal azide or even a fluorescein moiety at the sulfonylamide N atom (P2' substituent) were almost as active as the lead structure 1, making the latter derivative a suitable fluorescence imaging tool.
Topics: Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinase 2; Structure-Activity Relationship; Valine; Carboxylic Acids
PubMed: 37270903
DOI: 10.1016/j.bmc.2023.117350 -
Drugs Jul 2017Valbenazine (Ingrezza™) is an orally bioavailable, selective, vesicular monoamine transporter 2 (VMAT2) inhibitor being developed by Neurocrine Biosciences for the... (Review)
Review
Valbenazine (Ingrezza™) is an orally bioavailable, selective, vesicular monoamine transporter 2 (VMAT2) inhibitor being developed by Neurocrine Biosciences for the treatment of various central nervous system disorders. Valbenazine has been approved in the USA for the treatment of adults with tardive dyskinesia (TD), is at various stages of development in other countries for TD and is in phase 2 development in the USA for Tourette syndrome. This article summarizes the milestones in the development of valbenazine leading to its first global approval in the USA for the treatment of adults with TD.
Topics: Adult; Clinical Trials as Topic; Drug Approval; Humans; Tardive Dyskinesia; Tetrabenazine; Tourette Syndrome; United States; United States Food and Drug Administration; Valine; Vesicular Monoamine Transport Proteins
PubMed: 28578484
DOI: 10.1007/s40265-017-0770-9 -
Annales de Dermatologie Et de... May 2002Valaciclovir is an aciclovir pro-drug considerably improving its oral availability. Its antiviral activity in vivo is related to that of aciclovir, the principle target... (Review)
Review
Valaciclovir is an aciclovir pro-drug considerably improving its oral availability. Its antiviral activity in vivo is related to that of aciclovir, the principle target of which is the herpes virus. Following digestive absorption, valaciclovir is rapidly transformed into aciclovir. The mean absolute bioavailability of aciclovir is of 54.2% after a single oral dose of 1,000 mg of valaciclovir, i.e., a bioavailability 3 to 5-fold greater than after oral ingestion of aciclovir. The plasma pharmacokinetic profile of valaciclovir and aciclovir observed in volunteers infected by HIV is superimposable on that of healthy subjects. In elderly patients, exposure to aciclovir is enhanced, probably because of the alteration in glomerular filtration. In patients exhibiting agranulocytosis following poly-chemotherapy, the pharmacokinetic parameters are superimposable on those observed in healthy patients. In patients with hepatic failure, there appears no need to adapt the dose, since exposure to aciclovir does not appear altered. However, the dose of valaciclovir must be adapted to renal function. During the first-episode of herpes genitalis, valaciclovir, at the dose of 500 or 1,000 mg twice daily, is as effective as 200 mg of aciclovir five times per day. In recurrent herpes genitalis, 500 mg twice daily of valaciclovir is as effective as 1,000 mg twice daily or 200 mg five times a day of aciclovir. Valaciclovir prevents recurrence herpes genitalis with a dose-dependent effect, and doses of 500 and 1,000 mg/day are as effective as 400 mg twice daily of aciclovir. There are few studies on the efficacy of valaciclovir in the treatment of oro-facial herpes. In the treatment of herpes zoster in patients aged over 50, the principle benefit provided by valaciclovir at the dose of 1,000 mg twice daily, is the decrease in the percentage of patients presenting post-zoster pain and its duration. High doses of valaciclovir (8 capsules/day) provide efficient prevention of infections related to the cyto-megalo-virus (CMV) in immunodepressed patients due to HIV infection or following renal transplantation. Tolerance to valaciclovir, like its active metabolite aciclovir, is generally good. Central neurological toxicity is frequently observed with high doses, but regresses on withdrawal. The official indications in France are the curative and preventive treatment of herpes genitalis infections, the prevention of post-zoster pain and the ocular complications of ophthalmologic herpes in immunocompetent adults, and the prevention of CMV infections after organ grafting.
Topics: Acyclovir; Humans; Prodrugs; Valacyclovir; Valine; Virus Diseases
PubMed: 12124513
DOI: No ID Found -
Poultry Science Mar 2019An experiment was conducted to evaluate the total Valine (Val) requirement of first cycle laying hens from 41 to 60 wk of age. A total of 270 Hy-line W-36 laying hens...
An experiment was conducted to evaluate the total Valine (Val) requirement of first cycle laying hens from 41 to 60 wk of age. A total of 270 Hy-line W-36 laying hens were randomly assigned to 6 treatments with 15 replicate groups of 3 birds for each experimental unit. A Val deficient basal diet was formulated with corn and peanut meal with analyzed Val, Lys and crude protein concentrations of 0.515, 0.875, and 13.38%, respectively. Synthetic L-Val was supplemented to the basal diet in 0.070% increments to generate experimental diets containing 0.515, 0.585, 0.655, 0.725, 0.795, and 0.865% Val respectively. A controlled feeding program was applied during the experiment resulting in approximately 95 g feed intake per hen per day. Linear broken line, quadratic broken line, quadratic polynomial and exponential models were used to estimate the Val requirement of the hens based on hen-housed egg production (HHEP), egg mass (EM), and feed conversion ratio (FCR). Hen-housed egg production ranged from 48.3 to 81.4%, dependent upon dietary concentration of Val. Val requirements estimated by linear broken line, quadratic broken line, quadratic polynomial and exponential models were reported. Using the linear broken line model, the Val requirement was highest for egg mass, 597.3 mg/d, followed by egg production, 591.9 mg/d and lowest for FCR, 500.5 mg/d.
Topics: Animal Feed; Animals; Chickens; Diet; Eggs; Female; Oviposition; Valine
PubMed: 30329096
DOI: 10.3382/ps/pey448 -
The Journal of Biological Chemistry Jul 1976To explore the role of the pool of intracellular free valine in the processes of protein synthesis and protein degradation, cultured hepatoma (HTC) cells were incubated...
To explore the role of the pool of intracellular free valine in the processes of protein synthesis and protein degradation, cultured hepatoma (HTC) cells were incubated in media containing varying concentrations of L-valine, under conditions of constant rates of protein synthesis and protein breakdown, and at steady state levels of intracellular valine specific radioactivities. Two types of experiments were compared: in the first (designated "incorporation experiment"), unlabeled cells were exposed to [3H]valine for a short period of time. In the second (termed "reincorporation experiment"), cells were prelabled with [3H]valine and then incubated for a brief period with media containing different concentrations of unlabeled valine; reincorporation of [3H]valine was calculated by the difference between the release of [3H]valine from labeled cellular proteins at low valine concentrations, and the maximal rate of the release at high valine concentrations. In both types of experiments, the rates of [3H]valine incorporation or reincorporation were compared with the respective specific radioactivities of free intracellular valine. In the incorporation experiment, the rates of [3H]valine incorporation into protein calculated by the intracellular specific radioactivities were not constant, but showed an upward deviation at low valine concentrations. This is in agreement with the results of Mortimore, G.E., Woodside, K.H., and Henry, J.E. ((1972) J. Biol. Chem. 247, 2776-2784) in the perfused rat liver. By contrast, in the reincorporation experiment, the calculated rates of [3H]valine reincorporation based on intracellular specific radioactivities were constant throughout the range of valine concentrations. The constant value of calculated valine reincorporation was lower by 30 to 50% than the calculated rate of valine incorporation at high valine concentrations. The following model is proposed to explain these results. There is one common pool of free intracellular valine, but there are two sites where valyl-tRNA can be formed. The first is an internal site that utilizes valine from the intracellular pool, and the second is an external (possibly membranous) system that converts extracellular valine directly to valyl-tRNA. Valine originating from protein degradation flows into the intracellular pool, from which it can be reutilized by the internal system. According to these assumptions, in the incorporation experiment and at low valine concentrations, the specific activity of valyl-tRNA is higher than that of the intracellular pool of free valine, due to the contribution of the external system. On the other hand, in the reincorporation experiment the specific activity of extracellular valine is negligible in comparison with that of the intracellular pool. Therefore, in this case the specific activity of valyl-tRNA is proportional to that of the intracellular pool, with a constant dilution by unlabeled valine of extracellular origin...
Topics: Cell Line; Kinetics; Lysine; Mathematics; Neoplasm Proteins; Protein Biosynthesis; Valine
PubMed: 932042
DOI: No ID Found