Search Results (129,274)

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia. Full article

African swine fever virus (ASFV) is a high-consequence pathogen that causes African swine fever (ASF), for which mortality rates can reach 90–100%, with death typically occurring within 14 days. ASF is currently a highly contagious pandemic disease responsible for extensive losses in pig production in multiple affected countries suffering from extended outbreaks. While a limited number of vaccines to prevent ASF are in use in south-east Asia, vaccines are not widely available, are only effective against highly homologous strains of ASFV, and must be used prior to an outbreak on a farm. Currently, there is no treatment for ASF and culling affected farms is the only response to outbreaks on farms to try and prevent spreading. CRISPR/Cas systems evolved as an adaptive immune response in bacteria and archaea that function by cleaving and disrupting the genomes of invading bacteriophage pathogens. CRISPR technology has since been leveraged into an array of endonuclease-based systems used for nucleic acid detection, targeting, genomic cleavage, and gene editing, making them particularly well-suited for development as sequence-specific therapeutic modalities. The programmability of CRISPR-based therapeutics offers a compelling new way to rapidly and specifically target pathogenic viral genomes simply by using different targeting guide RNAs (gRNA) as an adaptable antiviral modality. Here, we demonstrate for the first time a specific CRISPR/Cas9 multiplexed gRNA system that targets the African swine fever viral genome, resulting in sequence-specific cleavage, leading to the reduction in the viral load in infected animals, and subsequent recovery from an otherwise lethal dose of ASFV. Moreover, animals that recovered had protective immunity to subsequent homologous ASFV infection. Full article

For effective water purification, the combination of membrane separation and catalytic degradation technologies not only permits continuous pollutant degradation but also successfully reduces membrane fouling. In recent years, catalytic membranes (CMs) have garnered a lot of interest in the water treatment industry. The main benefits of CMs are methodically explained in this review, emphasizing the synergistic effect of membrane separation and catalysis. These benefits include stable catalyst loading achieved through membrane structure manipulation, nanoconfinement, and effective degradation of organic pollutants. The application of catalytic membranes in water treatment is then thoroughly summarized, and they are separated into five main groups based on their unique catalytic reaction mechanisms: ozone catalytic membranes, photocatalytic membranes, electrocatalytic membranes, Fenton-type catalytic membranes, and persulfate catalytic membranes. The mechanisms and performance characteristics of each kind of CM are looked at in greater detail. Finally, research directions and future prospects for water treatment using catalytic membranes are proposed. This review provides recommendations for future research and development to ensure the effective use of catalytic membranes in water treatment, in addition to providing a thorough examination of the advancements made in their application in the treatment of various wastewaters. Full article

In the Mediterranean region, the persimmon cultivar ‘Rojo Brillante’ may experience up to four waves of fruit drop. The first is a physiological event during fruit set that is common in woody species, while the subsequent waves are induced by rising temperatures and prolonged summer water stress. These summer drops represent the main limiting factor, leading to yield losses of up to 90%. Organ abscission is a complex process regulated by genetic, hormonal, nutritional, and environmental factors. We hypothesise that calcium (Ca) plays a protective role in the abscission zone (AZ) by inhibiting cell wall-degrading enzymes such as polygalacturonase (PG) and pectin methylesterases (PMEs). Calcium applications every 15 days from anthesis onwards significantly reduced fruit drop. Treatments preserved polar auxin transport—through DkPIN1 expression—and inhibited stage C of the abscission process, decreasing the relative expression of the DkIDL6 gene in the AZ. Moreover, PME and PG activities were significantly lower in Ca-treated fruits, confirming the stabilising effect of calcium on AZ integrity. In summary, pre-anthesis calcium sprays reduced premature fruit drop by about 30% under heat–drought stress by down-regulating key abscission genes (DkIDL6, DkPG20, DkPME41) and preserving cell wall integrity and fruit firmness, supporting the use of Ca treatments as a climate-smart approach to stabilise persimmon yield. Full article

Melanoma, in advanced stages, is the most invasive type of skin cancer, with currently available treatments showing limited efficiency. The number of melanoma cancer cases is expected to increase in the coming years, emphasizing the need for more efficient therapeutic strategies. The present study aimed to evaluate the potential of β-blockers, commonly used to treat cardiac conditions, to be repurposed for the treatment of melanoma. The effects of non-selective β-blockers (carvedilol and propranolol), β1 selective blockers (atenolol and metoprolol) and antineoplastics drugs (cisplatin and 5-fluorouracil) on the A375 melanoma cell line were studied, individually and in combined exposures, by assessing cell viability over a 72 h period. The 72 h half-maximal inhibitory concentrations (IC₅₀s) determined for A375 cells allow the ranking of toxicity as: cisplatin (2.46 (1.87–3.38) µM) > 5-fluorouracil (4.77 (4.48–5.07) µM) > carvedilol (16.91 (15.47–18.99) µM) > propranolol (58.03 (57.08–59.11) µM) > atenolol and metoprolol (β1 selective blockers that exhibited no significant effect on the cell’s viability). The effects of combined exposures were also studied. Metoprolol and carvedilol exhibited synergistic interactions with cisplatin at specific concentrations. Overall, the data highlight the concentration-dependent nature of mixture effects and support the potential application of β-blockers melanoma treatment. Full article

Objective: This study aimed to evaluate, through a network meta-analysis, the short- and long-term efficacy of both Western medical therapies and traditional Chinese medical therapy (acupuncture) in improving symptoms of shoulder pain. Methods: A comprehensive computer-based search was conducted in Embase, Cochrane Library, Web of Science, and PubMed databases for randomized controlled trials (RCTs) related to Western and Chinese medical treatments for shoulder pain measured by visual analogue scale (VAS) scores. All researchers independently screened and selected studies, extracted data, and assessed the risk of bias. Studies that met quality standards were analyzed using Stata 16.0 and Review Manager 5.4 software. Results: A total of 269 articles were retrieved, and 15 were ultimately included in the network meta-analysis, covering nine types of Western and Chinese medical therapies. The total sample size was 1114 cases, with 557 in an experimental group and 557 in a control group. In terms of reducing VAS scores at 4 weeks after treatment, sham acupuncture was significantly less effective than acupuncture (MD: 19.39; 95% CI: 0.66–38.12), indicating that acupuncture had a better short-term effect on pain relief at 4 weeks. In terms of reducing VAS scores at 12 weeks after treatment, sodium hyaluronate (hyaluronate) was more effective than physical therapy (PT) in reducing long-term pain (MD: −19.57; 95% CI: −37.23–−1.90); suprascapular nerve block (SSNB) (MD: −9.11; 95% CI: −16.02–−2.20) and arthroscopic capsular release (MD: −16.07; 95% CI: −30.16–−1.97) were also more effective than PT. The top three treatments in terms of clinical efficacy for painful shoulder conditions were hyaluronate, SSNB, and arthroscopic capsular release. Conclusions: For the treatment of shoulder pain, hyaluronate, SSNB, and arthroscopic capsular release showed greater potential long-term efficacy in pain reduction than PT, with hyaluronate showing the best effect. Full article

Cheddar cheese ripening creates favorable conditions for desired microbial changes but also allows survival and outgrowth of spores like Clostridium tyrobutyricum and Bacillus licheniformis, leading to late-blowing defects. In the first phase of the study, NSLAB dynamics were evaluated in the presence of spores, where pilot-scale cheeses (110 L) were produced in four treatments: control, T1 (BL), T2 (CT), and T3 (BL+CT), each inoculated at 2.0 Log₁₀ CFU/mL with spores. Results showed that SLAB declined from 8.0 to 0.2 Log₁₀ CFU/g, while NSLAB increased from 2.0 to 8.5 Log₁₀ CFU/g by the third month and remained stable thereafter. Spore counts reached 2.94 ± 0.02 (T2) and 2.48 ± 0.03 (T3) Log₁₀ CFU/g, with visible spoilage signs appearing after five months, indicating that native NSLAB populations were inadequate to control late-blowing defects. In this study, the effect of soluble fiber (inulin) in stimulating NSLAB was evaluated by incorporating 1% inulin into Cheddar cheese across four treatments: T1 (C SF), T2 (BL SF), T3 (CT SF), and T4 (BL+CT SF). Inulin addition resulted in significantly higher NSLAB counts (>10.5 Log₁₀ CFU/g) and suppressed spore levels (<0.91 ± 0.03 Log₁₀ CFU/g), with no spoilage observed. Inulin addition selectively enhanced beneficial NSLAB, suppressing spore-forming bacteria and preventing late-blowing defects without affecting cheese quality. This provides a natural, sustainable strategy to enhance microbial safety during Cheddar cheese ripening. Full article

Background/objective: Online platforms for sharing prescription drug experiences are becoming increasingly available, yet their validity as measures of patient satisfaction remains unclear. This study aimed to evaluate the potential of an online drug review system, WePharm, as a proxy for treatment satisfaction among older adults taking antihypertensive medications. Methods: A cross-sectional survey using a convenience sample was conducted from February to July 2018 among patients aged 50–80 years recruited from four senior welfare centers and one community pharmacy in Seoul. Participants completed both an online review via WePharm and a paper-based Treatment Satisfaction Questionnaire for Medication (TSQM). Satisfaction attributes included drug efficacy, side effects, convenience, affordability, and willingness to recommend. Pearson correlation coefficients and ANOVA were used to examine concordance and associated factors. Results: A total of 313 participants were included. Online review scores were significantly correlated with TSQM scores across all domains as follows: effectiveness (r = 0.451), side effects (r = 0.363), convenience (r = 0.285), and overall satisfaction (r = 0.256), all p < 0.0001. Key factors associated with satisfaction included region, stage of hypertension, income, duration of antihypertensive use, and comorbidity count. Conclusions: Online patient medication reviews, as implemented in WePharm, demonstrated moderate correlation with validated treatment satisfaction measures. These findings support the potential utility of online drug review systems as complementary tools for capturing real-world patient experience and informing shared decision-making in clinical practice, and as these findings were from a convenience sample, further research is expected with the aim of improving generalizability. Full article

Duropathies encompass a spectrum of disorders linked to spinal dural tears and cerebrospinal fluid (CSF) leaks, resulting in significant neurological manifestations. This review synthesizes the current literature on duropathies, focusing on their anatomical and pathophysiological aspects, including conditions such as superficial siderosis, spontaneous intracranial hypotension, and spinal cord herniation. The methodologies employed include comprehensive evaluations through neuroimaging techniques such as MRI and CT myelography, alongside clinical assessments of symptoms like ataxia, hearing loss, and cognitive impairment. Key findings highlight the prevalence of dural defects in patients with superficial siderosis and the association of persistent CSF leaks with various neurological impairments. The review emphasizes the need for a standardized diagnostic and therapeutic approach to enhance patient management and improve outcomes. By addressing the interrelated nature of these conditions, the study underscores the importance of early intervention to mitigate long-term neurological consequences. Overall, the findings advocate for further research to elucidate the mechanisms underlying duropathies and the development of effective treatment strategies, ultimately aiming to improve the quality of life for affected individuals. Full article

The current known data on the involvement of the peptidergic systems in breast cancer progression is overwhelmingly vast. Peptidergic systems are useful tools for imaging, diagnosis, prognosis and treatment of breast cancer. These systems play a crucial role in both basic and clinical breast cancer research by enabling the exploration of novel molecular mechanisms, signaling pathways, and the development of effective drug design strategies. Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1–7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin). This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration and invasion, induction of apoptosis, and anti-angiogenesis. Multiple strategies have been developed to combat breast cancer, including peptide receptor silencing; antibodies conjugated to specific signaling proteins; antibodies targeting specific peptide receptors or oncogenic peptides; and the use of peptides or peptide receptor agonists/antagonists loaded with antitumor cargo. Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9–39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review. Peptidergic systems have tremendous anti-breast-cancer clinical potential which must be exploited and developed. Taken together, the available data highlight the enormous promise of translational research into breast cancer and peptidergic systems for the development of effective treatments. A full understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment. Full article

The yield and quality have long been constraining factors for the sustainable cultivation of Glycyrrhiza uralensis. This study evaluated the effects of foliar applications of forchlorfenuron (CPPU) at different concentrations (0, 5, 10, 20, and 40 mg·L⁻¹) on plant growth and secondary metabolism through comprehensive analyses of photosynthesis, endogenous phytohormones, root biomass, and medicinal components. To ensure consumer safety, CPPU residue dynamics and associated health risks were also assessed. The 10 mg·L⁻¹ treatment yielded the most pronounced improvements, increasing root biomass by 46%, glycyrrhizic acid content by 92%, and liquiritin content by 98.7%. It also enhanced the activity of ribulose-1,5-bisphosphate carboxylase, thereby improving overall photosynthetic gas exchange capacity, and significantly stimulated the synthesis of zeatin, abscisic acid, and salicylic acid. Residue analysis showed that by the 56th day after treatment, the CPPU level in roots was merely 5.44 × 10⁻⁴ mg·kg⁻¹, with a half-life of 11.74 days. The resulting risk quotient (RQ) was below 0.01%, well under the safety threshold of 1, indicating negligible health risk to consumers. Our results demonstrate that the targeted application of CPPU offers a highly effective and safe strategy for enhancing both the productivity and commercial quality of G. uralensis. Full article

Objectives: Shengji Yuhong Ointment (SJYHO) is a classic Traditional Chinese Medicine prescription used for refractory wounds, yet its systemic pharmacological mechanisms remain unclear. This study aimed to identify its key active compounds and develop a simplified, effective topical formulation. Methods: We employed an integrated approach, combining network pharmacology and machine learning to screen the key constituents and core targets of SJYHO. The lead compound, glycyrrhizic acid, was formulated into a hydrogel (GA-Gel). Its therapeutic efficacy was evaluated in a full-thickness excisional wound model in Sprague-Dawley rats over 21 days, assessing healing kinetics, histology, and pain behavior. The interaction between glycyrrhizic acid and the identified target PPIA, along with its immunomodulatory effects, was validated through molecular docking, molecular dynamics simulation, and RT-qPCR. Results: Our integrated analysis identified PPIA as the core target and glycyrrhizic acid as a key bioactive component of SJYHO. Animal experiments demonstrated that GA-Gel significantly accelerated wound closure, which was driven by its multi-faceted actions: reducing inflammation, promoting collagen deposition, alleviating pain, and modulating late-stage angiogenesis. Mechanistically, we confirmed that glycyrrhizic acid stably binds to PPIA. Furthermore, GA-Gel treatment mediated wound immune infiltration by specifically regulating CD8⁺ T cells, neutrophils, and memory B cells, an effect that was dependent on PPIA targeting. Conclusions: This study demonstrates that glycyrrhizic acid, formulated as GA-Gel, recapitulates the wound-healing benefits of SJYHO by specifically targeting PPIA and modulating the immune microenvironment. Our findings not only elucidate a key mechanistic pathway but also present GA-Gel as a rationally designed, clinically translatable therapy for acute and chronic wounds. Full article

Since individual embryos cannot be evaluated in group culture, establishing a single culture from in vitro maturation to in vitro culture may provide new insights into oocyte and embryo quality. This study aimed to develop a single culture system for individual oocytes, from in vitro maturation through fertilization to embryo development. The effects of curcumin supplementation during in vitro maturation on oocyte maturation, embryo development, and embryo quality were examined in single and group culture systems. Porcine oocytes were cultured individually in 20 µL microdroplets, with one oocyte per droplet, or in groups of 50 oocytes per 500 µL. The maturation medium contained curcumin at concentrations of 20 µM or less. Supplementation with 10 µM curcumin increased oocyte maturation in both systems compared to the controls. The fertilization rates and oocyte/embryo quality did not differ among the treatment groups. Oocytes matured with 10 µM curcumin in a single culture showed a higher blastocyst formation rate (7.0%) than the control (2.3%). In the group culture, 10 µM curcumin increased cleavage rates compared to the control (75.2% vs. 63.0%), but blastocyst formation rates did not differ. Blastocyst formation rates were similar between single and group cultures under control (2.3% and 4.3%, respectively) or 10 µM curcumin (7.0% and 11.4%, respectively) conditions. Therefore, porcine oocytes can develop to the blastocyst stage in a single culture system. Incorporating antioxidants during in vitro maturation may be an effective condition for in vitro embryo culture that can be implemented in a single oocyte. Full article

Epilobium parviflorum Schreb. is used in folk and modern medicine for the treatment of prostate diseases. It is also known to alleviate gastrointestinal ailments. The aim of the present study is to define the chemical composition of diverse extracts from the herb, to test their inhibitory properties toward post-proline-specific peptidases and to elucidate the mechanisms of their antitumor activity on colorectal carcinoma cells in vitro. The extractions were performed using mono- or biphasic systems of solvents. Their chemical compositions were defined by LC-HRMS. Inhibitory properties towards prolyloligopeptidase (POP) and fibroblast activation protein (FAP) were studied by kinetic assays on human recombinant enzymes. Antioxidant activity was measured by three methods. Genotoxicity to HT-29 colorectal carcinoma cells was analyzed with the comet assay. FACS analyses and flow cytometry were used to evaluate the extracts effect on the cell cycle and their pro-apoptotic properties on HT-29 cells. The extract derived using 80% ethanol was chosen for the next studies due to its efficient and selective inhibition of POP. It contains mainly oenotein B and myricetin-3-O-rhamnoside. Its antioxidant and moderate genotoxic activities can contribute to the antitumor effect on HT-29 cells. The extract has a small effect on the cell cycle but a pronounced pro-apoptotic action on those cells. In conclusion, the 80% ethanol extract of E. parviflorum concentrates the ellagitannin oenotein B, which is a selective inhibitor of POP. Antitumor activity of the extract towards HT-29 cells may be due to the inhibition of POP, the antioxidant, genotoxic and pro-apoptotic activities. Full article

Downy mildew, caused by Plasmopara halstedii, is a major threat to sunflower production worldwide, leading to severe yield losses. Since resistance in sunflower hybrids can be easily broken by the pathogen, it is important to find alternative and sustainable control methods against this disease. This study investigated the potential use of NeemAzal^®-T/S (a neem-based biopesticide formulation) to induce antioxidant defense responses in sunflower seedlings inoculated with P. halstedii (pathotype 704). Its effects, alone, or in combination with a reduced dose of Mefenoxam, were evaluated under controlled conditions. Plant height, sporulation, antioxidant enzyme activities (SOD, CAT, APX, POX, and PPO), lipid peroxidation (MDA), and hydrogen peroxide (H₂O₂) contents were measured. Our results indicate that the antioxidant responses of seedlings varied according to the treatment. MDA levels decreased even when NeemAzal^®-T/S was applied alone, while H₂O₂ production only decreased when both treatments were applied combined. Overall, NeemAzal^®-T/S can be a valuable alternative strategy to help control sunflower downy mildew, since it reduced sporulation and MDA content, and increased APX, POX, and PPO activities even at a later stage of infection in susceptible seedlings. These findings indicate that NeemAzal^®-T/S can activate defense mechanisms associated with oxidative stress reduction in sunflower, offering a promising strategy to help manage downy mildew in a more sustainable manner. Full article