Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin-Antitoxin System.

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

Lysine Distinctively Manipulates Myogenic Regulatory Factors and Wnt/Ca2+ Pathway in Slow and Fast Muscles, and Their Satellite Cells of Postnatal Piglets.

Muscle regeneration, representing an essential homeostatic process, relies mainly on the myogenic progress of resident satellite cells, and it is modulated by multiple physical and nutritional factors. Here, we investigated how myogenic differentiation-related factors and pathways respond to the first limiting amino acid lysine (Lys) in the fast and slow muscles, and their satellite cells (SCs), of swine. Thirty 28-day-old weaned piglets with similar body weights were subjected to three diet regimens: control group (d 0-28: 1.31% Lys, n = 12), Lys-deficient group (d 0-28: 0.83% Lys, n = 12), and Lys rescue group (d 0-14: 0.83% Lys; d 15-28: 1.31% Lys, n = 6). Pigs on d 15 and 29 were selectively slaughtered for muscular parameters evaluation. Satellite cells isolated from fast (semimembranosus) and slow (semitendinosus) muscles were also selected to investigate differentiation ability variations. We found Lys deficiency significantly hindered muscle development in both fast and slow muscles via the distinct manipulation of myogenic regulatory factors and the Wnt/Ca2+ pathway. In the SC model, Lys deficiency suppressed the Wnt/Ca2+ pathways and myosin heavy chain, myogenin, and myogenic regulatory factor 4 in slow muscle SCs but stimulated them in fast muscle SCs. When sufficient Lys was attained, the fast muscle-derived SCs Wnt/Ca2+ pathway (protein kinase C, calcineurin, calcium/calmodulin-dependent protein kinase II, and nuclear factor of activated T cells 1) was repressed, while the Wnt/Ca2+ pathway of its counterpart was stimulated to further the myogenic differentiation. Lys potentially manipulates the differentiation of porcine slow and fast muscle myofibers via the Wnt/Ca2+ pathway in opposite trends.

Rosacea treatment with mussel adhesive protein delivered via microneedling: In vivo and clinical studies.

BACKGROUND: Rosacea is a prevalent chronic dermatological condition marked by facial inflammation and erythema, significantly compromising the quality of life for affected individuals. Current treatment methods for rosacea are not considered ideal because of the complex etiology of the disease. Mussel adhesive protein (MAP) is a glycoprotein derived from the foot gland of mussels. The protein exhibits anti-inflammatory properties, relieves skin itching, and promotes wound healing. AIMS: We aimed to explore the feasibility of using MAP administered via microneedle delivery for treating rosacea and the potential molecular mechanism involved. MATERIALS AND METHODS: The therapeutic effect and mechanism of MAP microneedle delivery in an LL-37-induced rosacea-like mouse model were observed using morphological and histological methods. Twenty-seven patients with erythematotelangiectatic rosacea (ETR) underwent treatment once every 1 month, with three treatments constituting one treatment course. The therapeutic effect was evaluated by comparing the clinical images taken at baseline, after the first treatment course, and after the second treatment course. The red value, CEA, and GFSS score were also calculated. RESULTS: In response to the microneedle delivery of MAP, innate immunity, inflammatory infiltration, and abnormal neurovascular regulation improved significantly in rosacea-like mice. In the clinical experiments, the microneedle delivery of MAP significantly improved the symptoms of erythema, flushing, and telangiectasia in patients with ETR, and no obvious adverse reactions were observed. CONCLUSIONS: MAP delivered by microneedling is effective and safe for treating ETR.

Analysis of the efficacy of blunt separation combined with uncrosslinked sodium hyaluronate composite solution for the treatment of tear trough deformity in Asians.

BACKGROUND: Filling therapy is becoming increasingly popular for correcting tear trough deformities (TTD). However, its therapeutic effect and retention time are limited. AIMS: To improve the clinical efficacy and safety of TTD treatment in Asians, we used a blunt separation technique to break the adhesion site of periorbital subcutaneous tissue, and while repairing skin dermis after injury, it was combined with uncrosslinked hyaluronic acid compound solution to promote collagen regeneration and treat TTDs. PATIENTS/METHODS: Twenty-six Chinese patients (21 women and 5 men) with TTD, with a mean age of 34.54 ± 9.21 (range, 20-56) years, were enrolled. Symptom improvement, recurrence rates, treatment safety, and patient satisfaction were evaluated. RESULTS: All patients' tear trough rating scale (TTRS) scores decreased significantly immediately after treatment. The TTRS scores at 1, 3, and 6 months, and 1 year after treatment demonstrated significant differences from those before treatment (all p < 0.05). All patients' experienced mild pain, erythema, and swelling during the treatment. Three patients developed postinjection bruising after treatment, which lasted for 6-7 days and subsequently disappeared. No other adverse reactions were observed during the follow-up. There were no recurrent cases, and patient satisfaction was very high. CONCLUSIONS: Blunt separation combined with an uncrosslinked sodium hyaluronate composite solution is safe and effective for treating TTDs in Asians with few side effects and has good clinical application prospects.

Domain swapping of the C-terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis.

Polyketide metabolism-associated proteins in Mycobacterium tuberculosis play an essential role in the survival of the bacterium, which makes them potential drug targets for the treatment of tuberculosis (TB). The novel ribonuclease protein Rv1546 is predicted to be a member of the steroidogenic acute regulatory protein-related lipid-transfer (START) domain superfamily, which comprises bacterial polyketide aromatase/cyclases (ARO/CYCs). Here, we determined the crystal structure of Rv1546 in a V-shaped dimer. The Rv1546 monomer consists of four α-helices and seven antiparallel ß-strands. Interestingly, in the dimeric state, Rv1546 forms a helix-grip fold, which is present in START domain proteins, via three-dimensional domain swapping. Structural analysis revealed that the conformational change of the C-terminal α-helix of Rv1546 might contribute to the unique dimer structure. Site-directed mutagenesis followed by in vitro ribonuclease activity assays was performed to identify catalytic sites of the protein. This experiment suggested that surface residues R63, K84, K88, and R113 are important in the ribonuclease function of Rv1546. In summary, this study presents the structural and functional characterization of Rv1546 and supplies new perspectives for exploiting Rv1546 as a novel drug target for TB treatment.

Chemical composition of pigeon crop milk and factors affecting its production: a review.

Pigeons are important commercial poultry in addition to being ornamental birds. In 2021, more than 111 million pairs of breeding pigeons were kept in stock and 1.6 billion squabs were slaughtered for meat in China. However, in many countries, pigeons are not domestic birds; thus, it is necessary to elucidate the factors involved in their growth and feeding strategy due to their economic importance. Pigeons are altricial birds, so feedstuffs cannot be digested by squabs, which instead are fed a mediator named pigeon crop milk. During lactation, breeding pigeons (both female and male) ingest diets and generate crop milk to feed squabs. Thus, research on squab growth is more complex than that on chicken and other poultry. To date, research on the measurement of crop milk composition and estimation of the factors affecting its production has not ceased, and these results are worth reviewing to guide production. Moreover, some studies have focused on the formation mechanism of crop milk, reporting that the synthesis of crop milk is controlled by prolactin and insulin-activated pathways. Furthermore, the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathway, target of rapamycin (TOR) pathway and AMP-activated protein kinase (AMPK) pathway were also reported to be involved in crop milk synthesis. Therefore, this review focuses on the chemical composition of pigeon crop milk and factors affecting its production during lactation. This work explores novel mechanisms and provides a theoretical reference for improving production in the pigeon industry, including for racing, ornamental purposes, and production of meat products.

Mussel adhesive protein treatment delivered by microneedling for sensitive skin: A clinical study.

BACKGROUND: Mussel adhesive protein (MAP) is extracted from the mycelial glands of marine mussels. It has anti-inflammatory properties and may relieve skin itching and other symptoms. AIMS: Based on the anti-inflammatory effect of MAP, this study was designed to treat sensitive skin (SS) using MAP delivered by skin microneedling. PATIENTS/METHODS: Twenty-three Chinese female patients with SS were enrolled. Treatments were delivered three times at one-month intervals. Symptom improvement and recurrence rates, treatment safety, and patient satisfaction levels were evaluated. RESULTS: After one course of treatment, 20 patients had a Symptom Score Reducing Index (SSRI) of >20%, with an effectiveness rate of 87%. At the end of treatment, all patients had an SSRI of >20%, and the effectiveness rate was 100%. Dryness, tightness, desquamation, flushing, burning, itching, and tingling improved. After treatment, the Clinical Erythema Assessment and Lesion Severity Index of Facial Telangiectasia scores were significantly decreased. Clinical photographs following treatment revealed improved erythema reaction and decreased capillary density. During treatment, the patients experienced mild pain and erythema and swelling reaction without exudation. Complications, such as pigmentation changes or scarring, were absent. Additionally, there were no cases of recurrence, and patient satisfaction levels were high. CONCLUSION: MAP combined with microneedling can help treat SS, showing satisfactory safety outcomes and high patient satisfaction.

Effective of a novel technique for sensitive skin treatment with optimal pulse technology: A clinical study.

BACKGROUND AND AIMS: Photomodulation is a non-photothermal effect that mobilizes energy and regulates cell activity at the mitochondrial level, and has been used to treat sensitive skin (SS) in recent years. Based on the photomodulated effect of optimal pulse technology (OPT), we developed a novel treatment mode (advanced OPT with low energy, three pulses, long pulse width, AOPT-LTL) for the treatment of facial SS and evaluated its effectiveness. METHODS: A total of thirty Chinese women with SS were included in this study. Patients were received different times of AOPT-LTL treatment with an interval of 2 to 4 weeks depending on the severity. Clinical improvement was evaluated by comparing baseline and post-treatment photographs. In addition, the skin objective signs and subjective symptoms, as well as adverse events and patient satisfaction were also analyzed and tabulated. RESULTS: All included patients completed the treatment and follow-up period. After one course of treatment, 76.7% of patients had a Symptom Score Reducing Index (SSRI) >20%, suggesting that the treatment was effective. Within two courses of treatment, all patients had SSRI >20%, demonstrating significant improvement in skin sensitivity. The analysis of clinical photographs showed that facial dryness, desquamation, flushing, and skin color significantly improved, capillary density decreased, the dilated capillaries were retracted. During the treatment period, no obvious adverse reactions occurred in any patients, and the patients' satisfaction was high. CONCLUSIONS: This novel technique of AOPT-LTL might be an effective and safe modality for the treatment of SS.

Novel technique for rosacea treatment using optimal pulse technology: In vivo and clinical studies.

BACKGROUND: Rosacea is a chronic inflammatory skin disease affecting the face, and the current treatment effect is not satisfactory. Based on the photomodulation of optimal pulse technology (OPT), we developed a novel treatment mode, namely, advanced OPT with low energy, three pulses, and long pulse width (AOPT-LTL). AIMS: We aimed to explore the feasibility and underlying molecular mechanisms of AOPT-LTL treatment in a rosacea-like mouse model. Furthermore, we evaluated the safety and efficacy in patients with erythematotelangiectatic rosacea (ETR). MATERIALS AND METHODS: Morphological, histological, and immunohistochemical analyses were used to investigate the efficacy and mechanisms of AOPT-LTL treatment in the LL-37-induced rosacea-like mouse model. Moreover, 23 patients with ETR were included and received different times of treatment at intervals of 2 weeks depending on the severity of their condition. The treatment effect was assessed by comparing clinical photographs at baseline, 1 week, and 3 months after treatment, combined with the red value, GFSS, and CEA scores. RESULTS: After the AOPT-LTL treatment of the mice, we observed that the rosacea-like phenotype, inflammatory cell infiltration, and vascular abnormalities were significantly ameliorated, and the expression of the core molecules of rosacea was significantly inhibited. In the clinical study, the AOPT-LTL treatment exerted satisfactory therapeutic effects on erythema and flushing of ETR patients. No serious adverse events were observed. CONCLUSIONS: AOPT-LTL is a safe and effective method for the treatment of ETR.

Iturin A Rescued STb-R-Induced Pork Skeletal Muscle Growth Restriction through the Hypothalamic-Pituitary-mTORC1 Growth Axis.

The engineered STb-Rosetta Escherichia coli (STb-R) was designed to investigate the effects of Iturin A on the skeletal muscle growth of weaned piglets. A total of 28 piglets were randomly divided into 4 groups (7 piglets per group): the control group (100 mL PBS), the Iturin A group (100 mL 320 mg/kg body weight (BW) Iturin A), the STb-R group (100 mL 1 × 1010 CFU/mL STb-R), and the Iturin A + STb-R group (100 mL 320 mg/kg BW Iturin A + 1 × 1010 CFU/mL STb-R). Compared with the control, STb-R-reduced body weight gain were rescued by Iturin A. The semimembranosus muscle weight recovered to normal level in the Iturin A + STb-R group. The level of relevant genes of the growth axis were elevated by Iturin A, including GHRH in the hypothalamus, GHRHR and GH in the pituitary, and GHR, IGF-1 and IGF-1R in the semimembranosus muscle. Moreover, Iturin A increased the mean fiber area and the number of proliferating cells in the semimembranosus muscle, which were decreased by STb-R. Additionally, the mTORC1 pathway was reactivated by Iturin A to relieve the suppression of STb-R. Collectively, the hypothalamic-pituitary growth axis-mediated Iturin A reactivated the mTORC1 pathway to rescue STb-R-restricted pork skeletal muscle growth.

Lysine Interacts with Frizzled7 to Activate ß-Catenin in Satellite Cell-Participated Skeletal Muscle Growth.

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/ß-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/ß-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/ß-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate ß-catenin to stimulate MuSCs in promoting skeletal muscle growth.

[Determination of 25 disinfection by-products in drinking water using liquid-liquid extraction and gas chromatography].

OBJECTIVE: To establish a liquid-liquid extraction and gas chromatography method for the determination of 7 kinds of haloacetaldehydes, 7 kinds of haloacetonitriles, 7 kinds of halonitromethanes and 4 kinds of haloacetamides in drinking water. METHODS: A liquid-liquid extraction gas chromatography technique was employed. Experimental parameters, such as capillary column type, inlet temperature, concentration of salting out reagent and sample pH were optimized to develop an analytical method, and then method validation was conducted. RESULTS: HP-5 MS UI column(30 m×0.25 mm, 0.25 µm), inlet temperature at 180 ℃, addition of 8 g sodium chloride in 50 mL water sample and pH 4-5 were chosen as the final parameters. Good correlation coefficients were obtained in the linear range of 0.20-15 µg/L, with r greater than 0.999.Methods detection limits were between 0.008-0.088 µg/L. When spiked concentration was 1.0 µg/L for pure water and tap water, the recoveries were 81%-106% and 75%-117%, respectively, and relative standard deviations were both less than 4%. When spiked concentration was 12 µg/L for pure water and tap water, the recoveries were 92%-101% and 86%-106%, respectively, and relative standard deviations were less than 4% and 2%, respectively. CONCLUSION: This method is simple, sensitive, and effective. It is suitable for simultaneous determination of 25 disinfection byproducts in drinking water.

Dietary supplementation with pioglitazone hydrochloride and l-carnosine improves the growth performance, muscle fatty acid profiles and shelf life of yellow-feathered broiler chickens.

The present study aimed to investigate the effects of dietary pioglitazone hydrochloride (PGZ) and l-carnosine (LC) supplementation on the growth performance, meat quality, antioxidant status, and meat shelf life of yellow-feathered broiler chickens. Five hundred broiler chickens were randomly assigned into 4 experimental diets using a 2 × 2 factorial arrangement with 2 PGZ supplemental levels (0 and 15 mg/kg) and 2 LC supplemental levels (0 and 400 mg/kg) in basal diets for 28 d. The feed-to-gain ratio decreased whereas the average daily gain increased with PGZ supplementation. Greater dressing percentages, contents of intramuscular fat (IMF) in breast and thigh muscles, C18:3n-6, C18:1n-9 and monounsaturated fatty acid (MUFA) percentages of thigh muscle were observed with PGZ addition. Additionally, significant synergistic effects between PGZ and LC on the C18:1n-9 and MUFA contents were found. Supplementation with LC decreased drip loss, cooking loss and total volatile basic nitrogen, and increased the redness (a∗) value, the superoxide dismutase and glutathione peroxidase activities in thigh muscles. Moreover, the malondialdehyde content decreased when diets were supplemented with LC, and there was a synergistic effect between PGZ and LC. Additionally, the mRNA abundance of lipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ), PPARγ co-activator 1α and fatty acid-binding protein 3, increased with PGZ supplementation, and relevant antioxidation genes, such as nuclear factor erythroid-2-related factor 2 and superoxide dismutase 1, were enhanced with LC supplementation. In conclusion, the results indicated that the supplementation of PGZ and LC could improve the growth performance, antioxidant ability, IMF content, and meat shelf life of yellow-feathered broiler chickens.

Structural and functional analysis of the Klebsiella pneumoniae MazEF toxin-antitoxin system.

Bacterial toxin-antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of Klebsiella pneumoniae at 2.3 Šresolution is presented. The K. pneumoniae MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes, namely, hydro-phobic and hydro-philic interactions. Compared with structural homologs, K. pneumoniae MazF shows distinct features in loops ß1-ß2, ß3-ß4 and ß4-ß5. It can be inferred that these three loops have the potential to represent the unique characteristics of MazF, especially various substrate recognition sites. In addition, K. pneumoniae MazF shows ribonuclease activity and the catalytic core of MazF lies in an RNA-binding pocket. Mutation experiments and cell-growth assays confirm Arg28 and Thr51 as critical residues for MazF ribonuclease activity. The findings shown here may contribute to the understanding of the bacterial MazEF TA system and the exploration of antimicrobial candidates to treat drug-resistant K. pneumoniae.

Second intention healing of nasal ala and dorsum defects in Asians.

BACKGROUND: Reconstruction of defects of nasal ala and dorsum after surgical excision presents a substantial challenge to dermatologic surgeons. Second intention healing is a simple and extremely useful method to optimize cosmesis after skin cancer removal. OBJECTIVES: This study reported the cosmetic outcomes after second intention healing of nasal ala and dorsum defects in Asians, and estimated the time to epithelialization and complete healing. MATERIALS AND METHODS: Fifteen defects (<1 cm in diameter) of the nasal ala and dorsum in 10 patients were allowed to heal by secondary intention. Cosmetic results were evaluated and the time to epithelialization and complete healing were recorded. RESULTS: Cosmetic outcomes were good to excellent in 80% of the defects; defects of the dorsum showed poorer cosmetic results than defects of the ala. The wounds needed 5-17 days (mean 11.3; SD ± 4.18) to complete epithelialization and 10-24 days (mean 17.7; SD ± 4.85) to heal completely. CONCLUSIONS: Second intention healing of small nasal ala and dorsum defects (<1 cm in diameter) in Asians produces satisfactory cosmetic results with a low complication rate.

Structure-based design of peptides that trigger Streptococcus pneumoniae cell death.

Toxin-antitoxin (TA) systems regulate key cellular functions in bacteria. Here, we report a unique structure of the Streptococcus pneumoniae HigBA system and a novel antimicrobial agent that activates HigB toxin, which results in mRNA degradation as an antibacterial strategy. In this study, protein structure-based peptides were designed and successfully penetrated the S. pneumoniae cell membrane and exerted bactericidal activity. This result represents the time during which inhibitors triggered S. pneumoniae cell death via the TA system. This discovery is a remarkable milestone in the treatment of antibiotic-resistant S. pneumoniae, and the mechanism of bactericidal activity is completely different from those of current antibiotics. Furthermore, we found that the HigBA complex shows a crossed-scissor interface with two intermolecular ß-sheets at both the N and C termini of the HigA antitoxin. Our biochemical and structural studies provided valuable information regarding the transcriptional regulation mechanisms associated with the structural variability of HigAs. Our in vivo study also revealed the potential catalytic residues of HigB and their functional relationships. An inhibition study with peptides additionally proved that peptide binding may allosterically inhibit HigB activity. Overall, our results provide insights into the molecular basis of HigBA TA systems in S. pneumoniae, which can be applied for the development of new antibacterial strategies. DATABASES: Structural data are available in the PDB database under the accession number 6AF4.

Structural and Functional Study of the Klebsiella pneumoniae VapBC Toxin-Antitoxin System, Including the Development of an Inhibitor That Activates VapC.

Klebsiella pneumoniae is one of the most critical opportunistic pathogens. TA systems are promising drug targets because they are related to the survival of bacterial pathogens. However, structural information on TA systems in K. pneumoniae remains lacking; therefore, it is necessary to explore this information for the development of antibacterial agents. Here, we present the first crystal structure of the VapBC complex from K. pneumoniae at a resolution of 2.00 Å. We determined the toxin inhibitory mechanism of the VapB antitoxin through an Mg2+ switch, in which Mg2+ is displaced by R79 of VapB. This inhibitory mechanism of the active site is a novel finding and the first to be identified in a bacterial TA system. Furthermore, inhibitors, including peptides and small molecules, that activate the VapC toxin were discovered and investigated. These inhibitors can act as antimicrobial agents by disrupting the VapBC complex and activating VapC. Our comprehensive investigation of the K. pneumoniae VapBC system will help elucidate an unsolved conundrum in VapBC systems and develop potential antimicrobial agents.

Knockdown of fibronectin extra domain B suppresses TGF-ß1-mediated cell proliferation and collagen deposition in keloid fibroblasts via AKT/ERK signaling pathway.

Keloids represent a dermal fibrotic disease characterized by excess collagen deposition and invasion of normal skin beyond the wound boundary, similar to malignant tumor features. Fibronectin extra domain B (EDB) is highly expressed in many tumors but has not been studied in keloids. The present study aimed to investigate the expression and the influence of EDB on keloid and elucidate the putative signaling pathway. We examined expression of EDB and the effects of EDB on fibroblast proliferation, apoptosis and the expression of the related proteins and genes. The level of phosphorylation of Smad, ERK, and AKT was estimated to elucidate the signaling pathways. The results showed that EDB in human keloid tissues and fibroblasts was overexpressed. EDB knockdown suppressed the cell proliferation of keloid fibroblasts (KFs) treated by transforming growth factor-ß1 (TGF-ß1). Also, the phosphorylation of Smad, ERK, and AKT in TGF-ß1-induced KFs was inhibited In addition, the low expression of pro-collagen-I (Col-I) and Col-III protein and mRNA level was observed in the siEDB group. EDB knockdown inhibited cell proliferation and suppressed collagen deposition in TGF-1-induced KFs. The underlying mechanism is the activation of TGF-ß1/Smad, ERK, and AKT signaling pathways. Together, the results suggested that EDB is a promising therapeutic target for keloid clinical treatment.

mTORC1-Mediated Satellite Cell Differentiation Is Required for Lysine-Induced Skeletal Muscle Growth.

Skeletal muscle is the primary source of protein for humans. However, the mechanisms of skeletal muscle growth, such as nutrition control, remain unknown. Moreover, the function of lysine (Lys) in controling skeletal muscle growth has gradually demonstrated that Lys is not only substantial for protein synthesis but also a signaling molecule for satellite cell (SC) activation. In the current work, the number of differentiated SCs in the longissimus thoracis muscle and the fusion index of SCs were both governed by Lys supplementation. Meanwhile, the myogenic regulatory factors and the mammalian target of rapamycin complex 1 (mTORC1) pathway showed the same tendencies of changes as the differentiation of SCs. After Lys was resupplemented with rapamycin, the mTORC1 pathway was inhibited and the differentiation ability of SCs was suppressed. Collectively, the results showed that the mTORC1-pathway-mediated SC differentiation was required for Lys-promoted skeletal muscle growth.

Lysine inhibits apoptosis in satellite cells to govern skeletal muscle growth via the JAK2-STAT3 pathway.

Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions. However, the precise mechanism of apoptosis in skeletal muscle remains unknown. The objective of this study was to investigate whether apoptosis could be regulated by lysine (Lys) supplementation and the potential mechanism. In this study, an isobaric tag for relative and absolute quantification (iTRAQ) proteomics analysis of the longissimus dorsi muscle from piglets showed that the Janus family tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was involved in Lys deficiency-induced apoptosis and inhibited skeletal muscle growth. Meanwhile, western blotting results demonstrated that Lys deficiency led to apoptosis in the longissimus dorsi muscle with the JAK2-STAT3 pathway inhibition. Interestingly, apoptosis was suppressed, and the JAK2-STAT3 pathway was reactivated after Lys re-supplementation. In addition, the results showed that Lys deficiency-induced apoptosis in satellite cells (SCs) was mediated by the JAK2-STAT3 pathway inhibition. Moreover, the JAK2-STAT3 pathway was reactivated by Lys re-supplementation and suppressed cell apoptosis, and this effect was inhibited after treatment with Tyrphostin B42 (AG 490). In conclusion, we found that Lys inhibits apoptosis in SCs to govern skeletal muscle growth via the JAK2-STAT3 pathway.