Search Results (51)

Cuscutae Semen (CS), a traditional herb recognized as a nutraceutical food in China, has been widely utilized in managing aging-related diseases throughout history. However, whether this mechanism is associated with mitochondrial stress tolerance remains unclear. In the present study, Caenorhabditis elegans (C. elegans) was used to investigate the effects of CS on their longevity. The data demonstrated that CS prolonged the average lifespan of the nematodes by 15.26%, reducing lipofuscin accumulation by 61.46%, as well as improving spontaneous motility. CS treatment significantly enhanced the resistance of C. elegans to hydrogen peroxide-induced oxidative stress and 37 °C induced heat stress, reducing reactive oxygen species (ROS) production by 71.45%. Additionally, membrane potential (MMP) and adenosine triphosphate (ATP) were increased by 354.72% and 69.64%, respectively. However, mitochondrion-specific ROS and calcium flux were significantly reduced to 45.86% and 63.25%, respectively, in C. elegans treated with CS. Consistently, the polymerase chain reaction data revealed that CS significantly up-regulated the expressions of the antioxidant-related genes skn-1, ctl-1, sod-3, and gst-4; the heat shock gene hsp-16.2; and the autophagy-related genes lgg-1 and bec-1. Considering the crucial role of the silent information regulator sirtuin 1 (SIR-2.1/SIRT1) in aging-related mitochondrial oxidative stress, we examined its expression and transcriptional activity. As expected, treatment with CS induced SIRT1 expression, and isorhamnetin identified from CS extract significantly enhanced SIRT1 transcriptional activity in HEK293T cells. Collectively, our results provided evidence that CS prolonged the lifespan of C. elegans by ameliorating oxidative stress damage and mitochondrial dysfunction via SIRT1. Full article

Mammalian spermatozoa undergo a series of physiological and biochemical changes in the oviduct that lead them to acquire the ability to fertilize eggs. During their transit in the oviduct, spermatozoa face a series of environmental changes that can affect sperm viability. A series of ion channels and transporters, as well as the sperm cytoskeleton, allow spermatozoa to remain viable and functional. Cl⁻ channels such as TMEM16A (calcium-activated chloride channel), CFTR (cystic fibrosis transmembrane conductance regulator), and ClC3 (chloride voltage-gated channel 3) are some of the ion transporters involved in maintaining cellular homeostasis. They are expressed in mammalian spermatozoa and are associated with capacitation, acrosomal reaction, and motility. However, little is known about their role in maintaining sperm volume. Therefore, this study aimed to determine the mechanism through which TMEM16A maintains sperm volume during capacitation. The effects of TMEM16A were compared to those of CFTR and ClC3. Spermatozoa were capacitated in the presence of specific TMEM16A, CFTR, and ClC3 inhibitors, and the results showed that only TMEM16A inhibition increased acrosomal volume, leading to changes within the acrosome. Similarly, only TMEM16A inhibition prevented actin polymerization during capacitation. Further analysis showed that TMEM16A inhibition also prevented ERK1/2 and RhoA activation. On the other hand, TMEM16A and CFTR inhibition affected both capacitation and spontaneous acrosomal reaction, whereas ClC3 inhibition only affected the spontaneous acrosomal reaction. In conclusion, during capacitation, TMEM16A activity regulates acrosomal structure through actin polymerization and by regulating ERK1/2 and RhoA activities. Full article

Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived F_oF₁-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded F_oF₁-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30–40 μm vs. 15–25 μm in untreated). These results highlight the ATM’s potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity. Full article

Background: Modern societies and policymakers increasingly emphasize the advancement of organic farming practices and the preservation of rural culture. Sheep farming faces several challenges, including environmental impacts, antibiotic usage, and public concerns regarding animal welfare. The purpose of this study was to investigate the effects of Melissa officinalis extract and its principal phenolic acids on the motility of the sheep jejunum and colon, with the goal of assessing their potential as health-promoting feed additives, particularly in animals with dysmotilities. Methods: The trials were performed on isolated jejunum and colon preparations collected from sheep undergoing routine slaughter. The effect of extracts from Melissa Officinalis and three major phenolic acids (rosmarinic, chlorogenic, and lithospermic) was evaluated to identify their ability to modify the spontaneous and pharmacologically-induced contractility of circular and longitudinal smooth muscle. Results: Regarding spontaneous contractions: Melissa officinalis extract, rosmarinic acid, and lithospermic acid caused a significant decrease in spontaneous contractility in the jejunum and colon, while chlorogenic acid exhibited myocontractile effects except for colon circular preparations where the effect was myorelaxant as in the other acids. In the case of ACh-induced contractions, all acids and the Melissa officinalis extract caused mostly a significant decrease in the magnitude of acetylcholine-induced contractions in both longitudinal and circular smooth muscle strips of the colon and jejunum. Conclusions: The findings suggest a predominantly myorelaxant effect of the Melissa officinalis extract and its major phenolic acids on the smooth muscle of the sheep jejunum and colon. These results underscore the potential application of the Melissa officinalis extract as a feed additive to modulate intestinal motility and address challenges in livestock production. Full article

Probiotics have attracted increasing attention due to their benefits in terms of relieving gastrointestinal ailments, including constipation. This study evaluated the potential of Weizmannia coagulans BC99 for clinical remission of constipation in adults. In this randomized, double-blind, and placebo-controlled trial, 90 individuals with constipation were divided between a BC99 and a placebo group for an 8-week intervention duration. The spontaneous bowel movement (SBM) frequency, patient assessment of constipation symptoms (PAC-SYM), patient assessment of constipation quality of life (PAC-QOL), inflammatory cytokines, neurotransmitters, and serum metabolites were investigated before and after the intervention. The results showed that BC99 intervention significantly improved constipation symptoms and quality of life in adults with constipation, as evidenced by an increased SBM score and decreased PAC-SYM and PAC-QOL scores. Additionally, BC99 supplementation increased the levels of neurotransmitters (5-HT, MTL, AChE, and BDNF) associated with intestinal motility and alleviated inflammation in participants with constipation, as supported by higher levels of anti-inflammatory factors (IL-4, IL-10) and lower levels of pro-inflammatory factors (IL-6, IFN-γ) in the BC99 group. Furthermore, BC99 altered the abundance of 93 metabolites and affected biological pathways correlated with gastrointestinal motility, including sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. This study demonstrates the effectiveness of the W. coagulans BC99 strain in relieving constipation in adults, and reveals its potential mechanism of action. These findings provide a scientific basis for BC99 as an effective and safe probiotic for constipation treatment. Full article

Background: Three herbal extracts (Asparagus racemosus Willd., Tabebuia avellanedae Lorentz, and Glycyrrhiza glabra L.) were mixed with three essential oils (Foeniculum vulgare Mill., Mentha piperita L., and Pimpinella anisum L.) to formulate a product (HEMEO) whose active compounds include saponins and steroids in Asparagus racemosus, known for their anti-inflammatory properties; glycyrrhizin and flavonoids in Glycyrrhiza glabra, which exhibit gastroprotective and antispasmodic effects; menthol in Mentha piperita, contributing with antispasmodic and antimicrobial properties; and anethole and polyphenols in Pimpinella anisum, which modulate intestinal motility and offer antimicrobial activity. Objective: HEMEO was formulated for applications in intestinal motility disorders. Methods: HEMEO was evaluated for spontaneous and induced motility effects in isolated guinea pig ileum, colon, and stomach. Ex vivo experiments were conducted using LabChart software v7.0, and the product’s antibacterial action against Helicobacter pylori and its antioxidant effects were assessed through disc diffusion and FRAP assays. The presence of the volatile compounds in the formulation was confirmed by GC-MS analysis; the TPC of HEMEO, determined using the Folin–Ciocalteu method, was 9.925 ± 0.42 mg GAE/g. Conclusions: HEMEO showed a phenolic content correlated with its antioxidant potential and in addition inhibited H. pylori growth and demonstrated notable antioxidant properties, suggesting its role as a supportive agent in digestive processes and in managing motility disorders. Full article

Erwinia amylovora, the causal agent of fire blight, poses a serious threat to several rosaceous plants, especially apples and pears. In this study, a spontaneous streptomycin-resistant E. amylovora strain (EaSmR) was isolated under laboratory conditions. Compared with the parental strain TS3128, the EaSmR strain exhibited high resistance to streptomycin (>100,000 µg/mL) and showed a significant reduction in both swimming and swarming motility. To investigate the mechanisms underlying streptomycin resistance, the genome of EaSmR was sequenced, and four single nucleotide variants (SNVs) were identified in comparison with the EaSmR genome with TS3128. Two genes in EaSmR were found to contain SNVs relative to TS3128, including a point mutation at codon 43 in the rpsL gene, the primary target of streptomycin, which was identified as the cause of the resistance. Additionally, three other point mutations were detected within the gene encoding type I methionyl aminopeptidase (MetAP1), resulting in an amino acid substitution from serine to valine (S76V). Furthermore, we analyzed the nonsynonymous single nucleotide variants (nsSNVs) between the EaSmR isolate and the reference type strain, CFBP1430. A total of 111 nsSNVs were found in EaSmR, including three stop-gain mutations, across 102 genes, which likely account for potential differences between the Korean strain TS3128 (EaSmR) and the reference strain CFBP1430. Whole-genome sequencing of EaSmR reveals significant genetic changes and provides valuable insights into the role of single nucleotide variants in antibiotic resistance and altered physiological traits. As the first report of a laboratory-induced, streptomycin-resistant E. amylovora strain from South Korea, this study provides essential insights into resistance mechanisms and highlights key genomic differences that may contribute to the unique characteristics of the Korean strain, establishing a valuable foundation for future disease management strategies. Full article

Background: Prokinetic agents are effective in increasing gastrointestinal (GI) contractility and alleviating constipation, often caused by slow intestinal motility. Lubiprostone (LUB), known for activating CLC-2 chloride channels, increases the chloride ion concentration in the GI tract, supporting water retention and stool movement. Despite its therapeutic efficacy, the exact mechanisms underlying its pharmacological action are poorly understood. Here, we investigated whether LUB activates the canonical transient receptor potential cation channel type 4 (TRPC4) through stimulation with E-type prostaglandin receptor (EP) type 3. Methods: Using isotonic tension recordings on mouse colon strips, we examined LUB-induced contractility in both proximal and distal colon segments. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine mRNA levels of EP1-4 receptor subtypes in distal colonic muscular strips and isolated myocytes. The effects of a TRPC4 blocker and EP3 antagonist on LUB-stimulated contractions were also evaluated. Results: LUB showed significant contraction in the distal segment compared to the proximal segment. EP3 receptor mRNA levels were highly expressed in the distal colon tissue, which correlated with the observed enhanced contraction. Furthermore, LUB-induced spontaneous contractions in distal colon muscles were reduced by a TRPC4 blocker or EP3 antagonist, indicating that LUB-stimulated EP3 receptor activation may lead to TRPC4 activation and increased intracellular calcium in colonic smooth muscle. Conclusions: These findings suggest that LUB improves mass movement through indirect activation of the TRPC4 channel in the distal colon. The segment-specific action of prokinetic agents like LUB provides compelling evidence for a personalized approach to symptom management, supporting the defecation reflex. Full article

Background: A major issue in Chronic Myeloid Leukemia (CML) is the persistence of quiescent leukemia stem cells (LSCs) in the hematopoietic niche under tyrosine kinase inhibitor (TKI) treatment. Results: Here, using CFSE sorting, we show that low-proliferating CD34+ cells from CML patients in 3D co-culture hide under HS27A stromal cells during TKI treatment—a behavior less observed in untreated cells. Under the same conditions, Ba/F3p210 cells lose their spontaneous motility. In CML CD34+ and Ba/F3p210 cells, while Rac1 is completely inhibited by TKI, RhoA remains activated but is unable to signal to ROCK. Co-incubation of Ba/F3p210 cells with TKI, SKF-96365 (a calcium channel inhibitor), and EGF restores myosin II activation and amoeboid motility to levels comparable to untreated cells, sustaining the activation of ROCK. In CFSE+ CD34+ cells containing quiescent leukemic stem cells, co-incubation of TKI with SKF-96365 induced the expulsion of these cells from the HS27A niche. Conclusions: This study underscores the role of RhoA in LSC behavior under TKI treatment and suggests that SKF-96365 could remobilize quiescent CML LSCs through reactivation of the RhoA/ROCK pathway. Full article

Antispasmodic agents are crucial in managing gastrointestinal motility disorders by modulating muscle contractions and reducing symptoms like cramping and diarrhea. This study investigated the antispasmodic potential of different coffee bean extracts, including light coffee (LC), medium coffee (MC), and dark coffee (DC), on ileum contractions induced by potassium chloride (KCl), and elucidated their mechanisms of action using in vitro isolated tissue techniques. The results demonstrated that all coffee extracts reduced spontaneous contractions of rat ileum tissue in a dose-dependent manner. Among these, LC showed the most significant reduction in ileum contractions, particularly at higher concentrations. The key findings reveal that LC at 5 mg/mL significantly reduced CaCl₂-induced contractions in isolated rat ileum tissue, indicating that LC may inhibit calcium influx or interfere with calcium signaling pathways. The presence of nifedipine, propranolol, and N-nitro-L-arginine methyl ester (L-NAME) have been confirmed in their involvement; they block calcium influx and calcium channels and activate β-adrenergic pathways as part of LC’s mechanism of action. The presence of their active compounds, particularly chlorogenic acid and caffeine, likely contributes to the observed antispasmodic effects. These findings suggest that LC exerts its antispasmodic effects by targeting key mechanisms involved in muscle spasms and intestinal motility, providing a potential for managing such conditions. Full article

Parkinson’s disease (PD) is the second-most common neurodegenerative disorder worldwide and is diagnosed based on motor impairments. Non-motor symptoms are also well-recognised in this disorder, and peripheral neuropathy is a frequent but poorly appreciated non-motor sign. Studying how central and peripheral sensory systems are affected can contribute to the development of targeted therapies and deepen our understanding of the pathophysiology of PD. Although the cause of sporadic PD is unknown, chronic exposure to the pesticide rotenone in humans increases the risk of developing the disease. Here, we aimed to investigate whether peripheral neuropathy is present in a traditional model of PD. Mice receiving intrastriatal rotenone showed greatly reduced dopamine terminals in the striatum and a reduction in tyrosine hydroxylase-positive neurons in the Substantia nigra pars compacta and developed progressive motor impairments in hindlimb stepping and rotarod but no change in spontaneous activity. Interestingly, repeated testing using gold-standard protocols showed no change in gut motility, a well-known non-motor symptom of PD. Importantly, we did not observe any change in heat, cold, or touch sensitivity, again based upon repeated testing with well-validated protocols that were statistically well powered. Therefore, this traditional model fails to replicate PD, and our data again reiterate the importance of the periphery to the disorder. Full article

The fourth industrial revolution extensively reshapes the reality we are living in by blurring the boundaries of physical, digital and biological worlds. A good example is the previously unthinkable incursion of nanoscale waste materials, such as soot, into the technologies for assisted reproduction. Although the rapeseed oil soot may efficiently enhance the progressive motility of human spermatozoa, it is yet unknown whether this material induces undesirable oxidative stress and premature acrosome reaction, endangering the sperm-oocyte fusion and blastocyst formation. In an attempt to clarify this issue, we reveal that the three-hour incubation of human semen mixed with three main types of soot does not cause oxidative stress and spontaneous acrosome reaction of the sperm. These unique findings are attributed to synchronous elimination and stabilization of the oxidants via hydrogen bonding to the acidic groups of the soot (i.e., C=O and/or C-O-C) and electron donation by its basic chemical sites (i.e., C-OH and/or COOH). Moreover, the soot nanoparticles are electrostatically attracted by discrete positively charged areas on the sperm head, increasing its negative charge and in some cases interfering the acrosome reaction. Such novel mechanistic insights emphasize the credibility of rapeseed oil soot to confidently shift from the purely diagnostic and therapeutic phases in reproductive medicine to research dealing with the effect of carbon nanomaterials on the embryo development and implantation. Full article

Glucagon-like peptide-2 (GLP-2) has been reported to influence gastrointestinal motor responses, exerting a modulatory role on enteric neurotransmission. To our knowledge, no data on GLP-2 effects on the motility of the isolated ileum are available; therefore, we investigated whether GLP-2 affects the contractile activity of mouse ileal preparations and the neurotransmitters engaged. Ileal preparations showed tetrodotoxin (TTX)- and atropine-insensitive spontaneous contractile activity, which was unaffected by the nitric oxide synthesis inhibitor, L-NNA. GLP-2 depressed the spontaneous contractility, an effect that was abolished by TTX or L-NNA and not influenced by atropine. Electrical field stimulation induced TTX- and atropine-sensitive contractile responses, which were reduced in amplitude by GLP-2 even in the presence of L-NNA. Immunohistochemical results showed a significant increase in nNOS-positive fibers in the ileal muscle wall and a significant decrease in ChAT-positive myenteric neurons in GLP-2-exposed preparations. The present results offer the first evidence that GLP-2 acts on ileal preparations. The hormone appears to depress ileal contractility through a dual opposite modulatory effect on inhibitory nitrergic and excitatory cholinergic neurotransmission. From a physiological point of view, it could be hypothesized that GLP-2 inhibitory actions on ileal contractility can increase transit time, facilitating nutrient absorption. Full article

A synthetic pyrethroid pesticide, bifenthrin, has been commonly used as an effective exterminator, although the rise in its usage has raised concerns regarding its effects on the environment and public health, including reproduction, globally. The current study investigated the function-related molecular disparities and mechanisms in bifenthrin-exposed sperm cells and the underlying mechanism. Therefore, epididymal spermatozoa were released, and various concentrations of bifenthrin were treated (0.1, 1, 10, and 100 μM) to evaluate their effects on sperm. The findings showed that although bifenthrin had no effect on sperm viability, various other sperm functions (e.g., motility, spontaneous acrosome reaction, and capacitation) related to male fertility were decreased, commencing at a 1 µM treatment. Molecular studies revealed nine differentially expressed sperm proteins that were implicated in motile cilium assembly, sperm structure, and metabolic processes. Furthermore, bifenthrin affected sperm functions through abnormal diminution of the expression of specific sperm proteins. Collectively, these findings provide greater insights into how bifenthrin affects male fertility at the molecular level. Full article

In recent years, increasing attention has been paid to understanding the causes of infertility, which is being recognized as a growing health problem affecting large numbers of couples worldwide. Male infertility is a contributing factor in approximately 30–40% of cases, and one of its etiological causes is sexually transmitted infections (STIs). Among sexually transmitted pathogens, human papillomavirus (HPV) can contribute in various ways to the failure of spontaneous and assisted reproduction, acting in the different phases of conception, especially in the early ones. In particular, HPV infection can affect sperm DNA integrity, sperm motility, count, viability, and morphology and can induce the production of anti-sperm antibodies (ASAs). In this narrative review, we aimed to provide an overview of existing research on the potential adverse effects of HPV infection on male reproductive health. Furthermore, we analyzed how limiting the spread of the infection, particularly with gender-neutral vaccination, could be a possible therapeutic tool to counteract male and female fertility problems. Full article