Potato protein hydrolysate inhibits RANKL-induced osteoclast development by inhibiting osteoclastogenic genes via the NF-κB/MAPKs signaling pathways.

In recent times, there has been growing attention towards exploring the nutritional and functional aspects of potato protein, along with its diverse applications. In the present study, we examined the anti-osteoclast properties of potato protein hydrolysate (PP902) in vitro. Murine macrophages (RAW264.7) were differentiated into osteoclasts by receptor activator of nuclear factor-κB ligand (RANKL), and PP902 was examined for its inhibitory effect. Initially, treatment with PP902 was found to significantly prevent RANKL-induced morphological changes in macrophage cells, as determined by tartrate-resistant acid phosphatase (TRAP) staining analysis. This notion was further supported by F-actin analysis using a confocal microscope. Furthermore, PP902 treatment effectively and dose-dependently down-regulated the expression of RANKL-induced osteoclastogenic marker genes, including TRAP, CTR, RANK, NFATc1, OC-STAMP, and c-Fos. These inhibitory effects were associated with suppressing NF-κB transcriptional activation and subsequent reduced nuclear translocation. The decrease in NF-κB activity resulted from reduced activation of its upstream kinases, including I-κBα and IKKα. Moreover, PP902 significantly inhibited RANKL-induced p38MAPK and ERK1/2 activities. Nevertheless, PP902 treatment prevents RANKL-induced intracellular reactive oxygen species generation via increased HO-1 activity. The combined antioxidant and anti-inflammatory effects of PP902 resulted in significant suppression of osteoclastogenesis, suggesting its potential as an adjuvant therapy for osteoclast-related diseases.

Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis.

BACKGROUND: Metastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy. METHODS: We systematically searched Medline, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer, which is expressed as progression-free survival (PFS). In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Sixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR = 1.56, 95% CI = 1.19-2.03, I2 = 76.3%, P < 0.001). This result was further confirmed by trim-and-fill procedures and leave-one-out sensitivity analysis. CONCLUSIONS: This study suggests that sarcopenia may be a risk factor for reduced progression-free survival in patients with metastatic cancer. Further studies are still needed to explain the reason for this high heterogeneity in outcome. TRIAL REGISTRATION: CRD42022325910.

Neuroprotective Roles of Apelin-13 in Neurological Diseases.

Apelin is a natural ligand for the G protein-coupled receptor APJ, and the apelin/APJ system is widely distributed in vivo. Among the apelin family, apelin-13 is the major apelin isoform in the central nervous system and cardiovascular system, and is involved in the regulation of various physiopathological mechanisms such as apoptosis, neuroinflammation, angiogenesis, and oxidative stress. Apelin is currently being extensively studied in the nervous system, and apelin-13 has been shown to be associated with the onset and progression of a variety of neurological disorders, including stroke, neurodegenerative diseases, epilepsy, spinal cord injury (SCI), and psychiatric diseases. This study summarizes the pathophysiological roles of apelin-13 in the development and progression of neurological related diseases.

Ångstrom-scale silver particles ameliorate collagen-induced and K/BxN-transfer arthritis in mice via the suppression of inflammation and osteoclastogenesis.

OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.

At the limits of "capability": The sexual and reproductive health of women migrant workers in Malaysia.

Despite the centrality of sexual and reproductive health (SRH) to UN Sustainable Development Goals (SDGs), women migrant workers in Malaysia face an environment inimical to their SRH needs. Drawing on qualitative case study material, we present the first empirical application of the capability approach (CA) to explore the reproductive health needs of women migrant workers in a developing country, offering an original analysis of the capability for SRH of these women. Specifically, we explore the resources available to them; their opportunities and freedoms ("capabilities"); and factors that mediate transformation of resources into capability sets ("conversion factors"). While SRH information and health care are notionally available, women migrant workers face multiple challenges in converting resources into functionings, constraining the achievement of capability for SRH. Challenges include language barriers, personal beliefs, power relations between workers and employers and the consequences of current migration policy. We consider the scale of the challenges facing these women in securing SRH rights, the difficulties of operationalising the CA within such a setting, and the implications of our findings for the adequacy of the CA in supporting marginalised populations.

Principle active metabolites of Pinus morrisonicola Hayata synergistically inhibit cell proliferation and autophagy to elevate apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC), a common primary tumor of liver is a leading cause of cancer-associated deaths. Improving cellular apoptosis and enhancing autophagic clearance is been considered to improve treatment outcomes of HCC. Polyphenols from Pinus morrisonicola (Hayata) have shown various physiological and therapeutic benefits and the flavonoid chrysin is been known for their anticancer effects. However, the main bioactive principle and the mechanism underlying the antitumor activity of pine needle extract are not clear yet. In this study, the effects of ethanol extract from pine needle on HCC cells were determined. The results show that when compared with administration of chrysin alone, a fraction containing pinocembrin, chrysin, and tiliroside significantly reduced autophagy and increased apoptosis. The results also correlated with decrease in cell cycle regulators and the autophagic proteins like LC3-II. Collectively, the results imply the fraction containing pinocembrin, chrysin, and tiliroside as an ideal complementary medicine for an effective antitumor activity.

The Midfacial Soft Tissue Changes After Anterior Maxillary Segmental Distraction Osteogenesis in Patients With Cleft: A 3-Dimensional Volumetric-Based Subunit Analysis.

BACKGROUND: Maxillary hypoplasia is common in patients with cleft lip and palate. In this study, the authors investigated the soft tissue changes in midfacial regions after anterior maxillary segmental distraction osteogenesis (AMSDO) in patients with cleft. METHODS: Eight patients with cleft lip and palate who underwent AMSDO were enrolled in this study. Spiral computed tomographic images were taken before surgery and 6-12 months after surgery to evaluate soft tissue changes after AMSDO. The midfacial area was divided into 6 regions of interest according to anatomical subunits. The average movements of each region were calculated using volumetric changes and preoperative region surface areas. RESULTS: The upper lip on both sides has the most anterior movement (5.22±0.86 and 5.14±0.84 mm), supracommissural regions have a little less movement (4.11±0.55 and 3.81±0.67 mm), paranasal regions have the least movement (3.37±0.47 and 3.15±0.36 mm). The corresponding regions of interest showed no significant difference on the cleft side versus the noncleft side. CONCLUSIONS: Anterior maxillary segmental distraction osteogenesis can improve the soft tissue profile in patients with cleft, and there was no significant difference in soft tissue changes between the cleft side and the noncleft side.

Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration.

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

[Research progress of ferroptosis in hypoxia-associated brain injury].

Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.

PARD3 gene variation as candidate cause of nonsyndromic cleft palate only.

Nonsyndromic cleft palate only (NSCP) is a common congenital malformation worldwide. In this study, we report a three-generation pedigree with NSCP following the autosomal-dominant pattern. Whole-exome sequencing and Sanger sequencing revealed that only the frameshift variant c.1012dupG [p. E338Gfs*26] in PARD3 cosegregated with the disease. In zebrafish embryos, ethmoid plate patterning defects were observed with PARD3 ortholog disruption or expression of patient-derived N-terminal truncating PARD3 (c.1012dupG), which implicated PARD3 in ethmoid plate morphogenesis. PARD3 plays vital roles in determining cellular polarity. Compared with the apical distribution of wild-type PARD3, PARD3-p. E338Gfs*26 mainly localized to the basal membrane in 3D-cultured MCF-10A epithelial cells. The interaction between PARD3-p. E338Gfs*26 and endogenous PARD3 was identified by LC-MS/MS and validated by co-IP. Immunofluorescence analysis showed that PARD3-p. E338Gfs*26 substantially altered the localization of endogenous PARD3 to the basement membrane in 3D-cultured MCF-10A cells. Furthermore, seven variants, including one nonsense variant and six missense variants, were identified in the coding region of PARD3 in sporadic cases with NSCP. Subsequent analysis showed that PARD3-p. R133*, like the insertion variant of c.1012dupG, also changed the localization of endogenous full-length PARD3 and that its expression induced abnormal ethmoid plate morphogenesis in zebrafish. Based on these data, we reveal PARD3 gene variation as a novel candidate cause of nonsyndromic cleft palate only.

Integration of a multicomponent intervention for hypertension into primary healthcare services in Singapore-A cluster randomized controlled trial.

BACKGROUND: Despite availability of clinical practice guidelines for hypertension management, blood pressure (BP) control remains sub-optimal (<30%) even in high-income countries. This study aims to assess the effectiveness of a potentially scalable multicomponent intervention integrated into primary care system compared to usual care on BP control. METHODS AND FINDINGS: A cluster-randomized controlled trial was conducted in 8 government clinics in Singapore. The trial enrolled 916 patients aged ≥40 years with uncontrolled hypertension (systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg). Multicomponent intervention consisted of physician training in risk-based treatment of hypertension, subsidized losartan-HCTZ single-pill combination (SPC) medications, nurse training in motivational conversations (MCs), and telephone follow-ups. Usual care (controls) comprised of routine care in the clinics, no MC or telephone follow-ups, and no subsidy on SPCs. The primary outcome was mean SBP at 24 months' post-baseline. Four clinics (447 patients) were randomized to intervention and 4 (469) to usual care. Patient enrolment commenced in January 2017, and follow-up was during December 2018 to September 2020. Analysis used intention-to-treat principles. The primary outcome was SBP at 24 months. BP at baseline, 12 and 24 months was modeled at the patient level in a likelihood-based, linear mixed model repeated measures analysis with treatment group, follow-up, treatment group × follow-up interaction as fixed effects, and random cluster (clinic) effects. A total of 766 (83.6%) patients completed 2-year follow-up. A total of 63 (14.1%) and 87 (18.6%) patients in intervention and in usual care, respectively, were lost to follow-up. At 24 months, the adjusted mean SBP was significantly lower in the intervention group compared to usual care (-3.3 mmHg; 95% CI: -6.34, -0.32; p = 0.03). The intervention led to higher BP control (odds ratio 1.51; 95% CI: 1.10, 2.09; p = 0.01), lower odds of high (>20%) 10-year cardiovascular risk score (OR 0.67; 95% CI: 0.47, 0.97; p = 0.03), and lower mean log albuminuria (-0.22; 95% CI: -0.41, -0.02; p = 0.03). Mean DBP, mortality rates, and serious adverse events including hospitalizations were not different between groups. The main limitation was no masking in the trial. CONCLUSIONS: A multicomponent intervention consisting of physicians trained in risk-based treatment, subsidized SPC medications, nurse-delivered motivational conversation, and telephone follow-ups improved BP control and lowered cardiovascular risk. Wide-scale implementation of a multicomponent intervention such as the one in our trial is likely to reduce hypertension-related morbidity and mortality globally. TRIAL REGISTRATION: Trial Registration: Clinicaltrials.gov NCT02972619.

Association of genetic polymorphisms of VAX1, MAFB, and NTN1 with nonsyndromic cleft lip with or without cleft palate in Chinese population.

Nonsyndromic cleft lip with or without palate (NSCL/P) is a common birth defect involving genetic factors. We conducted this case-control study to verify the association of ten single-nucleotide polymorphisms (SNPs) of six genes (VAX1, MAFB, PAX7, ABCA4, NTN1, and NOG) with NSCL/P in the Chinese population. The study included 249 NSCL/P patients, 62 nonsyndromic cleft palate only (NSCPO) patients and 480 controls. Three loci, namely, VAX1 rs7078160, MAFB rs11696257, and NTN1 rs4791774, were associated with NSCL/P (Bonferroni method adjusted p values were 0.020, 0.00031, and 0.030, respectively). We also found that the disease risk of individuals carrying both VAX1 rs7078160 and NTN1 rs4791774 was higher than those carrying only one of them (p = 4.50 × 10-4 and 6.03 × 10-3, respectively). SNPs of genes VAX1 rs7078160, MAFB rs11696257, and NTN1 rs4791774 increased NSCL/P risk in the Chinese population.

Research Progress on Mechanism of Neuroprotective Roles of Apelin-13 in Prevention and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia. Currently, more than 50 million people live with dementia worldwide, and this number is expected to increase. Some of the typical pathological changes of AD include amyloid plaque, hyperphosphorylation of tau protein, secretion of inflammatory mediators, and neuronal apoptosis. Apelin is a neuroprotective peptide that is widely expressed in the body. Among members of apelin family, apelin-13 is the most abundant with a high neuroprotective function. Apelin-13/angiotensin domain type 1 receptor-associated proteins (APJ) system regulates several physiological and pathophysiological cell activities, such as apoptosis, autophagy, synaptic plasticity, and neuroinflammation. It has also been shown to prevent AD development. This article reviews the research progress on the relationship between apelin-13 and AD to provide new ideas for prevention and treatment of AD.

Dipeptide IF and Exercise Training Attenuate Hypertension in SHR Rats by Inhibiting Fibrosis and Hypertrophy and Activating AMPKα1, SIRT1, and PGC1α.

Bioactive peptides are physiologically active peptides produced from proteins by gastrointestinal digestion, fermentation, or hydrolysis by proteolytic enzymes. Bioactive peptides are resorbed in their whole form and have a preventive effect against various disease conditions, including hypertension, dyslipidemia, inflammation, and oxidative stress. In recent years, there has been a growing body of evidence showing that physiologically active peptides may have a function in sports nutrition. The present study aimed to evaluate the synergistic effect of dipeptide (IF) from alcalase potato protein hydrolysates and exercise training in hypertensive (SHR) rats. Animals were divided into five groups. Bioactive peptide IF and swimming exercise training normalized the blood pressure and decreased the heart weight. Cardiac, hepatic, and renal functional markers also normalized in SHR rats. The combined administration of IF peptide and exercise offer better protection in SHR rats by downregulating proteins associated with myocardial fibrosis, hypertrophy, and inflammation. Remarkably, peptide treatment alongside exercise activates the PI3K/AKT cell survival pathway in the myocardial tissue of SHR animals. Further, the mitochondrial biogenesis pathway (AMPKα1, SIRT1, and PGC1α) was synergistically activated by the combinatorial treatment of IF and exercise. Exercise training along with IF administration could be a possible approach to alleviating hypertension.

VH-4-A Bioactive Peptide from Soybean and Exercise Training Constrict Hypertension in Rats through Activating Cell Survival and AMPKα1, Sirt1, PGC1α, and FoX3α.

Hypertension is a chronic disease related to age, which affects tens of millions of people around the world. It is an important risk factor that causes myocardial infarction, heart failure, stroke, and kidney damage. Bioactive peptide VHVV (VH-4) from soybean has shown several biological activities. Physical exercise is a cornerstone of non-pharmacologic treatment for hypertension and has established itself as an effective and complementary strategy for managing hypertension. The present study evaluates the efficacy of VH-4 supplement and swimming exercise training in preventing hypertension in spontaneously hypertensive rats (SHR). SHR animals were treated with VH-4 (25 mg/kg by intraperitoneal administration) and swimming exercise (1 h daily) for eight weeks, and the hemodynamic parameters, histology, and cell survival pathway protein expression were examined. In SHR rats, increased heart weight, blood pressure, and histological aberrations were observed. Cell survival protein p-PI3K and p-AKT and antiapoptosis proteins Bcl2 and Bcl-XL expression decreased in SHR animals. SIRT1 and FOXO3 were decreased in hypertensive rats. Both bioactive peptide VH-4 treatment and swimming exercise training in hypertensive rats increased the cell survival proteins p-PI3K and p-AKT and AMPKα1, Sirt1, PGC1α, and FoX3α proteins. Soy peptide VH-4, along with exercise, acts synergistically and prevents hypertension by activating cell survival and AMPKα1, Sirt1, PGC1α, and FoX3α proteins.

Disturbances in Microbial and Metabolic Communication across the Gut-Liver Axis Induced by a Dioxin-like Pollutant: An Integrated Metagenomics and Metabolomics Analysis.

To determine how the aryl hydrocarbon receptor (AhR) signaling acts along the gut-liver axis, we employed an integrated metagenomic and metabolomic approach to comprehensively profile the microbial and metabolic networks. Adult zebrafish were exposed to a model agonist of the AhR: polychlorinated biphenyl (PCB) 126. The metagenomic analysis showed that PCB126 suppressed microbial activities related to primary bile acid metabolism in male intestines. Accordingly, a suite of primary bile acids consistently showed higher concentrations, suggesting that bacterial conversion of primary bile acids was blocked. PCB126 also disturbed bacterial metabolism of bile acids in female intestines, as revealed by higher concentrations of primary bile acids (e.g., chenodeoxycholic acid) and activation of the nuclear farnesoid X receptor signaling. In addition, PCB126 exposure impaired the metabolism of various essential vitamins (e.g., retinol, vitamin B6, and folate). Degradation of vitamin B6 by bacterial enzymes was inhibited in male intestines, resulting in its intestinal accumulation. However, PCB126 suppressed the bacterial metabolism of vitamins in female intestines, causing systematic deficiency of essential vitamins. Overall, we found that PCB126 exposure dysregulated gut microbial activities, consequently interrupting bile acid and vitamin metabolism along the gut-liver axis. The findings provided an insight of the AhR action in microbe-host metabolic communication related to PCBs.

An Observational Study to Evaluate Association Between Velopharyngeal Anatomy and Speech Outcomes in Adult Patients With Severe Velopharyngeal Insufficiency.

OBJECTIVE: By measuring velopharyngeal structure and evaluating speech intelligibility, to explore and observe the association between velopharyngeal anatomy and speech outcomes in these patients. METHODS: Thirty-one adult patients with velopharyngeal insufficiency after the primary palatoplasty aged 18 to 35 years (mean 22.03 years) were enrolled as the study group. The patients had significant hypernasality and audible nasal emission. The degree of velopharyngeal closure assessed by electronic nasopharyngeal fiberoptic endoscopy was grade III. Cephalometric analysis was performed on lateral cephalograms to measure velopharyngeal structure, including hard palate length (ANS-PNS), velar length (PNS-U), pharyngeal depth (PNS-PPW), and oropharyngeal airway space (U-MPW). Their speech intelligibility was evaluated through the Mandarin Chinese speech intelligibility test, and each speech sample was examined by 2 speech and language pathologists. The results were assessed with the SPSS 23.0 software package, and regression analysis was used to examine the relationship between velopharyngeal structure and speech outcomes. RESULTS: A significant negative correlation was confirmed between speech intelligibility and pharyngeal depth. Pharyngeal depth also showed a linear relationship with speech intelligibility, and there was no significant correlation between speech intelligibility and other measures (hard palate length, velar length, oropharyngeal airway space). CONCLUSIONS: In the velopharyngeal anatomy, only pharyngeal depth was associated with speech intelligibility in adult patients with severe velopharyngeal insufficiency, this is consistent with our clinical observation. It suggests that appropriate reduction of pharyngeal depth during palatopharyngoplasty may have a good effect on the speech recovery in patients with cleft palate and patients with velopharyngeal insufficiency after palatorrhaphy.

Alcalase Potato Protein Hydrolysate-PPH902 Enhances Myogenic Differentiation and Enhances Skeletal Muscle Protein Synthesis under High Glucose Condition in C2C12 Cells.

Sarcopenia is an aging associated disorder involving skeletal muscle atrophy and a reduction in muscle strength, and there are no pharmaceutical interventions available thus far. Moreover, conditions such as hyperglycaemia are known to further intensify muscle degradation. Therefore, novel strategies to attenuate skeletal muscle loss are essential to enhance muscle function and thereby improve the quality of life in diabetic individuals. In this study, we have investigated the efficiency of a potato peptide hydrolysate PPH902 for its cytoprotective effects in skeletal muscle cells. PPH902 treatment in C2C12 cells showed the dose-dependent activation of the Akt/mTOR signalling pathway that is involved in skeletal myogenesis. According to Western blotting analysis, PPH902 induced the phosphorylation of Akt, mTOR proteins and induced the myogenic differentiation of C2C12 myoblasts in a differentiation medium. The phosphorylation myogenic transcription factor Foxo3A was also found to be increased in the cells treated with PPH902. In addition, treatment with PPH902 ameliorated the high glucose induced reduction in cell viability in a dose-dependent manner. Moreover, the number of myotubes in a differentiation medium reduced upon high glucose challenge, but treatment with PPH902 increased the number of differentiated myotubes. Further, the phosphorylations of AMPK and mitochondrial-related transcription factors such as PGC-1α were suppressed upon high glucose challenge but PPH902 treatment restored the protein levels. We demonstrate, for the first time, that a specific potato peptide has a therapeutic effect against sarcopenia. In addition, PPH902 improved the myogenic differentiation and their mitochondrial biogenesis and further improved myogenic protein and inhibited muscle protein degradation in C2C12 cells challenged under a high glucose condition.

Bioactive peptides attenuate cardiac apoptosis in spontaneously hypertensive rat hearts through activation of autophagy and mitochondrial biogenesis pathway.

Alcalase potato protein hydrolysate (APPH) might have a very important role in therapeutic effects. This study aims to examine the beneficial effects of bioactive peptides (DIKTNKPVIF [DI] and IF) from APPH supplement in the regulation of cardiac apoptosis, autophagy, and mitochondrial biogenesis pathway in spontaneously hypertensive rats (SHR). We have investigated ejection fraction, fractional shortening, Tunel assay, apoptosis, autophagy, and mitochondrial biogenesis pathway marker expression to show the efficacy of bioactive peptides in an SHR model. Bioactive peptides significantly upregulate ejection fraction and fractional shortening in SHR rats. SHR rats exhibited higher protein expression of apoptotic markers such as BAD, cytochrome c, and caspase 3. Finally, the bioactive peptides upregulate survival proteins (p-AKT/p-PI3K), autophagy (Beclin1/LC3B), and mitochondrial biogenesis (p-AMPKα/SIRT1/PGC1α/p-Foxo3a/Nrf2/CREB) marker expressions compared with the SHR groups. In summary, the bioactive peptides protect the heart tissues through the activation of autophagy and mitochondrial biogenesis pathway and thereby attenuate cardiac apoptosis in a spontaneously hypertensive rat model.