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Abstract: Abstract In the human body, the skin is one of the organs most affected by the aging process. Nutritional approaches aimed to counteract the age-induced decline of extracellular matrix (ECM) deposition could be a valuable tool to decrease the degenerative processes underlying skin aging. Here, we investigated the ability of a six-amino acid plus hyaluronic acid (6AAH) formulation enriched with tricarboxylic acid (TCA) intermediates to stimulate ECM gene expression. To this aim, human BJ fibroblasts were treated with 6AAH alone or plus succinate or malate alone or succinate plus malate (6AAHSM), and mRNA levels of several ECM markers were evaluated. 6AAHSM increased the expression of all the ECM markers significantly above 6AAH alone or plus only succinate or malate. Furthermore, in an in vitro oxidative damage model, 6AAHSM blunted the hydrogen peroxide-induced decline in ECM gene expression. Our data suggest that feeding cells with 6AAH enriched with TCAs could efficiently be employed as a non-pharmacological approach for counteracting skin aging. PubDate: 2023-09-28
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Abstract: Abstract Plasma amino acid levels are altered upon many pathological conditions including acute pancreatitis. It is unclear whether amino acids can be used as specific biomarker of acute pancreatitis severity or recovery. Development of acute pancreatitis is associated with mitochondrial dysfunction and decreased cytosolic ATP level. Sodium pyruvate is considered as a potential treatment of pancreatitis due to its ability to sustain mitochondrial oxidative and ATP-productive capacity in vitro. This study investigated the effect of sodium pyruvate on pancreatic morphology and plasma amino acid levels in rats with acute pancreatitis. Acute pancreatitis in rats was induced by administration of l-arginine (5 g/kg) Experimental treatment group received sodium pyruvate (1 g/kg) for 4 days. On day 8 of the experiment, animals were killed, blood was collected and plasma amino acid concentration was determined with high-performance liquid chromatography. Histological examination showed large areas of fibrosis in the pancreas of animals treated with l-arginine irrespectively of sodium pyruvate administration. Sodium pyruvate improved the plasma amino acid levels. Rats with acute pancreatitis had significantly lower levels of most essential and non-essential amino acids and increased glutamate and aspartate in plasma. Administration of sodium pyruvate completely or partially restored the levels of methionine, phenylalanine, tryptophan, leucine, isoleucine, aspartate, asparagine and ornithine levels, while increasing glutamine and serine to levels significantly higher than control. Plasma lysine, alanine, arginine and taurine remained unaffected in all experimental groups. Sodium pyruvate may be considered for use as a maintenance therapy in acute pancreatitis. PubDate: 2023-09-27
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Abstract: Abstract The investigation was to determine the effect of camel milk fermented with Limosilactobacillus fermentum KGL4 (MTCC 25515) on ACE-inhibiting, anti-inflammatory, and diabetes-preventing properties and also to release the novel peptides with antidiabetic and anti-hypertensive attributes with molecular interaction studies. Growth conditions were optimised on the basis of total peptide production by inoculating the culture in camel milk at different rates (1.5, 2.0, and 2.5%) along with different incubation periods (12, 24, 36, and 48 h). However, after 48 h of fermentation with a 2.5% rate of inoculum, the highest proteolytic activity was obtained. Reverse phase high-pressure liquid chromatography (RP-HPLC) was used to calculate the % Rpa from permeates of 3 kDa and 10 kDa fractions. Molecular weight distributions of fermented and unfermented camel milk protein fractions were compared using SDS-PAGE. Spots obtained from 2D gel electrophoresis were separated on the basis of pH and molecular weight. Spots obtained from 2D gel were digested with trypsin, and the digested samples were subjected to RP-LC/MS for the generation of peptide sequences. The inhibition of tumour necrosis factor alpha, interleukin-6, and interleukin-1 during fermentation was studied using RAW 264.7 macrophages. In the study, fermented camel milk with KGL4 (CMKGL4) inhibited LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1β) by the murine macrophages. The results showed that the peptide structures (YLEELHRLNK and YLQELYPHSSLKVRPILK) exhibited considerable binding affinity against hPAM and hMGA during molecular interaction studies. PubDate: 2023-09-25
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Abstract: Abstract Postnatal muscle growth is impaired in low birth weight (L) neonatal pigs. Leucine supplementation has been established as a dietary intervention to enhance muscle growth in growing animals. The aim of this study was to investigate the efficacy of supplementing L neonatal pig formulas with branched-chain amino acids (B) to enhance the rate of protein accretion. Twenty-four 3-day old pigs were divided into two groups low (L) and normal birth weight (N) based on weight at birth. Pigs were assigned to a control (C) or 1% branched-chain amino acids (B) formulas, and fed at 250 mL·kg body weight −1·d−1 for 28 d. Body weight of pigs in the L group was less than those in the N group (P < 0.01). However, fractional body weight was greater for L pigs compared with their N siblings from day 24 to 28 of feeding regardless of formula (P < 0.01). In addition, feed efficiency (P < 0.0001) and efficiently of protein accretion (P < 0.0001) were greater for L than N pigs regardless of supplementation. Pigs fed the B formula had greater plasma leucine, isoleucine, and valine concentrations compared with those fed the C formula (P < 0.05). Longissimus dorsi Sestrin2 protein expression was less for pigs in the L group compared with those in the N group (P < 0.01), but did not result in a corresponding increase in translation initiation signaling. Longissimus dorsi mRNA expression of BCAT2 was less for LB pigs compared with those in the LC group, and was intermediate for NC and NB pigs (P < 0.05). Hepatic mRNA expression of BCKDHA was greater for pigs in the L compared with those in the N groups (P < 0.05). However, plasma branched-chain keto-acid concentration was reduced for C compared with those in the B group (P < 0.05). These data suggest that branched-chain amino acid supplementation does not improve lean tissue accretion of low and normal birth weight pigs, despite a reduction in Sestrin2 expression in skeletal muscle of low birth weight pigs. The modest improvement in fractional growth rate of low birth weight pigs compared with their normal birth weight siblings was likely due to a more efficient dietary protein utilization. PubDate: 2023-09-24
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Abstract: Abstract Insulin resistance is often accompanied by elevated circulating branched-chain amino acids (BCAA). We investigated the effects of insulin resistance on the mitochondrial BCAA transporter, SLC25A44, using a myotube model of insulin resistance. Insulin sensitivity and SLC25A44 expression were assessed via Western blot. Liquid chromatography-mass spectrometry was used to evaluate extracellular BCAA media content. Insulin resistance reduced pAkt activation following insulin stimulation but did not alter SLC25A44 expression. Under select conditions, insulin resistance led to the accumulation of extracellular BCAA. PubDate: 2023-09-23
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Abstract: Abstract Diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, is a major cause of mortality in patients. However, identifying circulatory markers to diagnose DKD requires a thorough understanding of the metabolic mechanisms of DKD. In this study, we performed ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to reveal altered metabolic profiles of amino acids (AAs) in patients with DKD. We found decreased plasma levels of histidine and valine, increased urine levels of proline, decreased urine levels of histidine and valine, and increased saliva levels of arginine in patients with DKD compared with the levels in patients with type 2 diabetes mellitus (T2DM) and in healthy controls. Our analyses of the key metabolites and metabolic enzymes involved in histidine and valine metabolism indicated that the AAs level alterations may be due to enhanced carnosine hydrolysis, decreased degradation of homocarnosine and anserine, enhanced histidine methylation, and systemic enhancement of valine metabolism in patients with DKD. Notably, we generated a distinct diagnostic model with an AUC of 0.957 and an accuracy up to 92.2% on the basis of the AA profiles in plasma, urine and saliva differing in patients with DKD using logistic regression and receiver operating characteristic analyses. In conclusion, our results suggest that altered AA metabolic profiles are associated with the progression of DKD. Our DKD diagnostic model on the basis of AA levels in plasma, urine, and saliva may provide a theoretical basis for innovative strategies to diagnose DKD that may replace cumbersome kidney biopsies. PubDate: 2023-09-22
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Abstract: Abstract Insect venom is abundant in potential antimicrobial peptides (AMPs), which can serve as novel alternatives to conventional antibiotics. Among them, Lasioglossin III LL-III) is a promising candidate with a broad spectrum against many fungi strains and both types of bacteria, whereas almost non-toxic to red blood cells. Many chemical approaches have been recently applied to improve its pharmacological properties and provide useful information regarding structure–activity relationships. Hence, this review focused on highlighting the lesson learned from each modification and supporting the future design of potent, selective, and metabolically stable AMPs. PubDate: 2023-09-22
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Abstract: Abstract Amino acids which are essential nutrients for all cell types’ survival are also recognised to serve as opportunistic/alternative fuels in cancers auxotrophic for specific amino acids. Accordingly, restriction of amino acids has been utilised as a therapeutic strategy in these cancers. Contrastingly, amino acid deficiencies in cancer are found to greatly impair immune functions, increasing mortality and morbidity rates. Dietary and supplemental amino acids in such conditions have revealed their importance as ‘immunonutrients’ by modulating cellular homeostasis processes and halting malignant progression. L-arginine specifically has attracted interest as an immunonutrient by acting as a nodal regulator of immune responses linked to carcinogenesis processes through its versatile signalling molecule, nitric oxide (NO). The quantum of NO generated directly influences the cytotoxic and cytostatic processes of cell cycle arrest, apoptosis, and senescence. However, L-lysine, a CAT transporter competitor for arginine effectively limits arginine input at high L-lysine concentrations by limiting arginine-mediated effects. The phenomenon of arginine–lysine antagonism can, therefore, be hypothesised to influence the immunonutritional effects exerted by arginine. The review highlights aspects of lysine’s interference with arginine-mediated NO generation and its consequences on immunonutritional and anti-cancer effects, and discusses possible alternatives to manage the condition. However, further research that considers monitoring lysine levels in arginine immunonutritional therapy is essential to conclude the hypothesis. PubDate: 2023-09-20
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Abstract: Abstract Recently, the serum levels of branched-chain amino acids (BCAAs) have been considered as an indicator to evaluate health status and predict chronic diseases risk. This systematic review and meta-analysis aimed to assess the relationship between Serum BCAAs and the risk of all-cause mortality. We carried out a comprehensive and systematic search in various important databases, including PubMed, Scopus, and Web of Science databases to find the relevant studies published up to October 2022 with no language, design, or time limitation. We extracted the reported hazard ratio (HR) with 95% confidence interval (CI) and odds ratio (OR) with 95%CI in cohorts and case–control studies, respectively, and computed the log HR or OR and its standard error. Then, we used the random-effects model with inverse variance weighting method for the present meta-analysis, to calculate the pooled effect size. Ten observational studies, including nine cohort studies and one case–control study, were included in the present meta-analysis. The number of participants ranges from 53 to 26,711, with an age range of 18–99 years. During 6 months to 24 years of follow-up, 3599 deaths were ascertained. The pooled results indicated that there was no significant association between serum BCAAs (RR: 1.17; 95% CI 0.85–1.60), isoleucine (RR: 1.41; 95%CI 0.92–2.17), leucine (RR: 1.13; 95% CI 0.94–1.36), and valine (RR: 1.02; 95%CI 0.86–1.22) and all-cause mortality. Also, there was significant heterogeneity between studies for serum BCAAs (I2 = 74.1% and P-heterogeneity = 0.021), isoleucine (I2 = 89.4% and P-heterogeneity < 0.001), leucine (I2 = 87.8% and P-heterogeneity < 0.001), and valine (I2 = 86.6% and P-heterogeneity < 0.001). Our results suggested that the serum BCAAs and its components, including isoleucine, leucine, and valine, were not associated with the risk of all-cause mortality. PubDate: 2023-09-19
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Abstract: Abstract Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC–MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe–Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance. PubDate: 2023-09-19
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Abstract: Abstract Amino acid metabolic profile, particularly its association with clinical characteristics, remains unclear in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) combined with metabolic disorders. In this study, we performed targeted metabolomic analyses on 64 patients with HIV/AIDS and 21 healthy controls. Twenty-four amino acids and selected intermediate metabolites in the serum were quantitatively detected using high-performance liquid chromatography–tandem mass spectrometry, and characteristic changes and metabolic pathways were analyzed in HIV-infected patients with different degrees of abnormal glucose and lipid metabolism. Spearman’s partial correlation was used to analyze the association between amino acids, biochemical parameters, and inflammatory cytokines. The results showed that the main metabolic pathways of the eighteen differential metabolites involved were arginine biosynthesis and metabolism, methionine cycle, and tryptophan metabolism. Fourteen differential amino acid metabolites were positively correlated with nine inflammatory cytokines, including TNF-α, C-reactive protein, IL-1β, and galectin-3 (FDR < 0.1). Kynurenine, ornithine, and homocysteine were positively correlated with fasting blood glucose and insulin resistance index (FDR < 0.1). Our study revealed a multi-pathway imbalance in amino acid metabolism in patients with HIV/AIDS, which was significantly correlated with inflammation and insulin resistance. PubDate: 2023-09-19
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Abstract: Abstract The emergence of antibiotic resistance prompts exploration of viable antimicrobial peptides (AMPs) designs. The present study explores the antimicrobial prospects of Apoptin nuclear localization sequence (NLS2)-derived peptide ANLP (PRPRTAKRRIRL). Further, we examined the utility of the NLS dimerization strategy for improvement in antimicrobial activity and sustained bio-stability of AMPs. Initially, the antimicrobial potential of ANLP using antimicrobial peptide databases was analyzed. Then, ANLP along with its two homodimer variants namely ANLP-K1 and ANLP-K2 were synthesized and evaluated for antimicrobial activity against Escherichia coli and Salmonella. Among three AMPs, ANLP-K2 showed efficient antibacterial activity with 12 µM minimum inhibitory concentration (MIC). Slow degradation of ANLP-K1 (26.48%) and ANLP-K2 (13.21%) compared with linear ANLP (52.33%) at 480 min in serum stability assay indicates improved bio-stability of dimeric peptides. The AMPs presented no cytotoxicity in Vero cells. Dye penetration assays confirmed the membrane interacting nature of AMPs. The zeta potential analysis reveals effective charge neutralization of both lipopolysaccharide (LPS) and bacterial cells by dimeric AMPs. The dimeric AMPs on scanning electron microscopy studies showed multiple pore formations on the bacterial surface. Collectively, proposed Lysine scaffold dimerization of Apoptin NLS2 strategy resulted in enhancing antibacterial activity, bio-stability, and could be effective in neutralizing the off-target effect of LPS. In conclusion, these results suggest that nuclear localization sequence with a modified dimeric approach could represent a rich source of template for designing future antimicrobial peptides. PubDate: 2023-09-19
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Abstract: Abstract Abnormal fat accumulation, enhanced free fatty acids (FFA) release, and their metabolites cause insulin resistance (IR) in major glucose-lipid metabolic organs such as skeletal muscle and adipose tissue. However, excessive lipolysis and FFA release from adipose tissue elevate plasma FFA levels leading to oxidative stress and skeletal muscle IR. Indeed, in obese individuals, there is enhanced pro-inflammatory secretion from adipose tissue influencing insulin signaling in skeletal muscles. Here, we investigated the effect of PSTi8 on FFA-induced IR in both in vitro and in vivo models. Palmitate (Pal)-treated 3T3-L1 cells increased lipid accumulation as well as lipolysis, which reduced the insulin-stimulated glucose uptake. PSTi8 treatment significantly prevented Pal-induced lipid accumulation, and release and enhanced insulin-stimulated glucose uptake. It further reduced the release of pro-inflammatory cytokines from Pal-treated 3T3-L1 cells as well as from adipose tissue explants. In addition, PSTi8 treatment decreases M1 surface markers in Pal-treated bone marrow-derived monocytes (BMDM). PSTi8 treatment also significantly enhanced the Pal-mediated reduced skeletal muscle glucose disposal and reduced intracellular oxidative stress. In vitro effect of PSTi8 was consistent with in vivo HFD-fed mice IR model. PSTi8 treatment in HFD-fed mice significantly improved glucose metabolism and enhanced skeletal muscle insulin sensitivity with reduced adiposity and pro-inflammatory cytokines. Taken together, our results support that PSTi8 treatment can protect both adipose and skeletal muscles from FFA-induced IR. PubDate: 2023-09-16
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Abstract: Abstract The minimal inhibitory concentrations (pMIC) are a valuable measure of the biological activity of polypeptides. Numerical data on the pMIC are necessary to systematize knowledge on polypeptides’ biochemical behaviour. The model of negative decimal logarithm of pMIC of polypeptides in the form of a mathematical function of a sequence of amino acids is suggested. The suggested model is based on the so-called correlation weights of amino acids together with the correlation weights of fragments of local symmetry (FLS). Three kinds of the FLS are considered: (i) three-symbol fragments ‘…xyx…’, (ii) four-symbol fragments ‘…xyyx…’, and (iii) five-symbol fragments ‘…xyzyx…’. The models built using the Monte Carlo technique improved by applying the index of ideality of correlation (IIC) and correlation intensity index (CII). PubDate: 2023-09-14
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Abstract: Abstract Proteins often possess several motifs and the ones with similar motifs were found to have similar biochemical properties and thus related biological functions. Thereby, multiple databases were developed to store information on such motifs in proteins. For instance, PDBsum stores the results of Promotif’s generated structural motifs and Pfam stores pre-computed patterns of functional domains. In addition to the fact that all this stored information is extremely useful, we can further augment its importance if we ought to integrate these motifs into visualization software. In this work, we have developed PyProtif, a plugin for the PyMOL molecular visualization program, which automatically retrieves protein structural and functional motifs from different databases and integrates them in PyMOL for visualization and analyses. Through an expendable menu and a user-friendly interface, the plugin grants the users the ability to study simultaneously multiple proteins and to select and manipulate each motif separately. Thus, this plugin will be of great interest for structural, evolutionary and classification studies of proteins. PubDate: 2023-09-12
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Abstract: Abstract Ventricular remodeling is one of the main causes of mortality from heart failure due to hypertension. Exploring its mechanism and finding therapeutic targets have become urgent scientific problems to be solved. A number of studies have shown that Mas, as an Ang-(1-7) specific receptor, was significantly reduced in myocardial tissue of rats undergoing hypertensive ventricular remodeling. It has been reported that Mas receptor levels are significantly downregulated in myocardium undergoing ventricular remodeling, but studies focused on intracellular and post-translational modifications of Mas are lacking. The results of this research are as follows: (1) PDZK1 interacts with the carboxyl terminus of Mas through its PDZ1 domain; (2) the expression of PDZK1 and Mas is decreased in rats undergoing hypertensive ventricular remodeling, and PDZK1 upregulation can ameliorate hypertensive myocardial fibrosis and myocardial hypertrophy; (3) PDZK1 enhances the stability of Mas protein through the proteasome pathway, and the proteasome inhibitor MG132 promotes hypertensive ventricular remodeling. PDZK1 improves ventricular remodeling in hypertensive rats by regulating Mas receptor stability. This study provides a scientific basis for the prevention and treatment of ventricular remodeling. PubDate: 2023-09-11
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Abstract: Abstract Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography–tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis. PubDate: 2023-09-10
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Abstract: Abstract Our recent study confirmed that the mature neuropeptide FAM237A, also known as neurosecretory protein GL (NPGL), is an efficient agonist for GPR83. The paralog FAM237B was previously reported as a weak agonist for GPR83. In the present study, we prepared mature human FAM237B via an intein-fusion approach and demonstrated that it could cause a significant activation effect at the nanomolar range (1‒10 nM) in a NanoBiT-based β-arrestin recruitment assay. Thus, FAM237B appears to be another endogenous agonist for GPR83 and future in vivo studies will be required to confirm this. PubDate: 2023-09-09
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Abstract: Abstract Peptides are short linear molecules consisting of amino acids that play an essential role in most biological processes. They can treat diseases by working as a vaccine or antimicrobial agent and serves as a cancer molecule to deliver the drug to the target site for the treatment of cancer. They have the potential to solve the drawbacks of current medications and can be industrially produced in large quantities at low cost. However, poor chemical and physical stability, short circulating plasma half-life, and solubility are some issues that need solutions before they can be used as therapeutics. PepAnalyzer tool is a user-friendly tool that predicts 15 different properties such as binding potential, half-life, transmembrane patterns, test tube stability, charge, isoelectric point, molecular weights, and molar extinction coefficients only using the sequence. The tool is designed using BioPython utility and has even results with standard tools, such as Expasy, EBI, Genecorner, and Geneinfinity. The tool assists students, researchers, and the pharmaceutical sector. The PepAnalyzer tool’s online platform is accessible at the link: http://www.iksmbrlabdu.in/peptool. PubDate: 2023-09-05
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Abstract: Abstract The emergence of drug-resistant superbugs has necessitated a pressing need for innovative antibiotics. Antimicrobial peptides (AMPs) have demonstrated broad-spectrum antibacterial activity, reduced susceptibility to resistance, and immunomodulatory effects, rendering them promising for combating drug-resistant microorganisms. This study employed computational simulation methods to screen and design AMPs specifically targeting ESKAPE pathogens. Particularly, AMPs were rationally designed to target the BamA and obtain novel antimicrobial peptide sequences. The designed AMPs were assessed for their antibacterial activities, mechanisms, and stability. Molecular docking and dynamics simulations demonstrated the interaction of both designed AMPs, 11pep and D-11pep, with the β1, β9, β15, and β16 chains of BamA, resulting in misfolding of outer membrane proteins and antibacterial effects. Subsequent antibacterial investigations confirmed the broad-spectrum activity of both 11pep and D-11pep, with D-11pep demonstrating higher potency against resistant Gram-negative bacteria. D-11pep exhibited MICs of 16, 8, and 32 μg/mL against carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and multi-drug-resistant Acinetobacter baumannii, respectively, with a concomitant lower resistance induction. Mechanism of action studies confirmed that peptides could disrupt the bacterial outer membrane, aligning with the findings of molecular dynamics simulations. Additionally, D-11pep demonstrated superior stability and reduced toxicity in comparison to 11pep. The findings of this study underscore the efficacy of rational AMP design that targets BamA, along with the utilization of D-amino acid replacements as a strategy for developing AMPs against drug-resistant bacteria. PubDate: 2023-09-05
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