Litchi pulp-derived gamma-aminobutyric acid (GABA) extract counteracts liver inflammation induced by litchi thaumatin-like protein.

Gamma-aminobutyric acid (GABA) is the predominant amino acid in litchi pulp, known for its neuroregulatory effects and anti-inflammatory properties. Although previous research has highlighted the pro-inflammatory characteristics of litchi thaumatin-like protein (LcTLP), interplay between GABA and LcTLP in relation to inflammation remains unclear. This study aims to explore the hepatoprotective effects of the litchi pulp-derived GABA extract (LGE) against LcTLP-induced liver inflammation in mice and LO2 cells. In vivo experiments demonstrated that LGE significantly reduced the levels of aspartate transaminase and alanine transaminase, and protected the liver against infiltration of CD4+ and CD8+ T cells and histological injury induced by LcTLP. Pro-inflammatory cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α were also diminished by LGE. The LGE appeared to modulate the mitogen-activated protein kinase (MAPK) signaling pathway to exert its anti-inflammatory effects, as evidenced by a reduction of 47%, 35%, and 31% in phosphorylated p38, JNK, and ERK expressions, respectively, in the liver of the high-dose LGE group. Additionally, LGE effectively improved the translocation of gut microbiota by modulating its microbiological composition and abundance. In vitro studies have shown that LGE effectively counteracts the increase in reactive oxygen species, calcium ions, and pro-inflammatory cytokines induced by LcTLP. These findings may offer new perspectives on the health benefits and safety of litchi consumption.

Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats.

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation.

Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification.

BACKGROUND: Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus, and the existing treatments cannot meet the needs of today's patients. Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application. However, the specific mechanism by which it works is still unclear. Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) for the treatment of DKD will provide a new way of thinking for the research and development of new drugs. AIM: To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking, and then verify the initial findings by in vitro experiments. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredient targets of NRDP. Targets for DKD were obtained based on the Genecards, OMIM, and TTD databases. The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram, and Cytoscape 3.9.0 was used to build a "drug-component-target-disease" network. The String database was used to construct protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology analysis were performed based on the DAVID database. After selecting the targets and the active ingredients, Autodock software was used to perform molecular docking. In experimental validation using renal tubular epithelial cells (TCMK-1), we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability, with glucose solution used to mimic a hyperglycemic environment. Flow cytometry was used to detect the cell cycle progression and apoptosis. Western blot was used to detect the protein expression of STAT3, p-STAT3, BAX, BCL-2, Caspase9, and Caspase3. RESULTS: A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP. Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products (AGEs)-receptor for AGEs (RAGE) signaling as the core pathway. Molecular docking showed good binding between each active ingredient and its core targets. In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells, blocked cell cycle progression in the G0/G1 phase, and reduced apoptosis in a concentration-dependent manner. Based on the results of Western blot analysis, NRDP differentially downregulated p-STAT3, BAX, Caspase3, and Caspase9 protein levels (P < 0.01 or P < 0.05). In addition, BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced, while BCL-2 and STAT3 protein expression was upregulated (P < 0.01). CONCLUSION: NRDP may upregulate BCL-2 and STAT3 protein expression, and downregulate BAX, Caspase3, and Caspase9 protein expression, thus activating the AGE-RAGE signaling pathway, inhibiting the vitality of TCMK-1 cells, reducing their apoptosis. and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Novel Hydrogel Adjuvant of Chinese Medicine External Preparations for Accelerated Healing of Deep Soft Tissue Injuries.

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.

Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

BACKGROUND: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE: This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS: We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS: This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS: Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55662.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

Resource utilization of stone waste and loess to prepare grouting materials.

Loess, a terrestrial clastic sediment, is formed essentially by the accumulation of wind-blown dust, while stone waste (SW) is an industrial waste produced during stone machining. Utilising loess and SW to prepare environmentally-friendly supplementary cementitious materials can not only address environmental issues caused by solid waste landfills but also meet the demand of reinforcement of coal-seam floor aquifer for grouting materials. In this paper, the effects of the loess/SW mass ratio and calcination temperature on the transformation of calcined products are investigated and their pozzolanic activities are evaluated. The workability, environmental impact and cost of grouting materials based on cement and calcined products are also assessed. Experimental results reveal that higher temperatures favour the formation of free lime and periclase, which tend to be involved in solid-state reactions. Higher temperature and loess/SW mass ratio strengthens the diffraction peaks of dodecalcium hepta-aluminate (C12A7), dicalcium ferrite (C2F) and dicalcium silicate (C2S). The clay minerals in loess become completely dehydroxylated before 825 °C, generating amorphous SiO2 and Al2O3. Covalent Si-O bonds are interrupted and that disordered silicate networks are generated in the calcined products, which is confirmed by the increased strength of the Si29 resonance region at -60 ppm to -80 ppm. Although co-calcined loess and SW contain the most four-fold aluminium at 950 °C, recrystallisation depresses the pozzolanic activity. Hence, the loess/SW sample designated LS2-825 exhibits the better hydration activity. Additionally, grouting materials composed of cement and LS2-825 exhibit good setting times, fluidity, strength and a low carbon footprint in practical engineering applications, and they also provide the additional benefit of being cost effective.

Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases.

Metabolic disorders, encompassing diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, etc., pose a substantial global health threat, with rising morbidity and mortality rates. Addressing these disorders is crucial, as conventional drugs often come with high costs and adverse effects. This review explores the potential of royal jelly (RJ), a natural bee product rich in bioactive components, as an alternative strategy for managing metabolic diseases. RJ exhibits diverse therapeutic properties, including antimicrobial, estrogen-like, anti-inflammatory, hypotensive, anticancer, and antioxidant effects. This review's focus is on investigating how RJ and its components impact conditions like diabetes mellitus, cardiovascular disease, and gastrointestinal illnesses. Evidence suggests that RJ serves as a complementary treatment for various health issues, notably demonstrating cholesterol- and glucose-lowering effects in diabetic rats. Specific RJ-derived metabolites, such as 10-hydroxy-2-decenoic acid (10-HDA), also known as the "Queen bee acid," show promise in reducing insulin resistance and hyperglycemia. Recent research highlights RJ's role in modulating immune responses, enhancing anti-inflammatory cytokines, and suppressing key inflammatory mediators. Despite these promising findings, further research is needed to comprehensively understand the mechanisms underlying RJ's therapeutic effects.

New insights into bee pollen: Nutrients, phytochemicals, functions and wall-disruption.

Bee pollen is hailed as a treasure trove of human nutrition and has progressively emerged as the source of functional food and medicine. This review conducts a compilation of nutrients and phytochemicals in bee pollen, with particular emphasis on some ubiquitous and unique phenolamides and flavonoid glycosides. Additionally, it provides a concise overview of the diverse health benefits and therapeutic properties of bee pollen, particularly anti-prostatitis and anti-tyrosinase effects. Furthermore, based on the distinctive structural characteristics of pollen walls, a substantial debate has persisted in the past concerning the necessity of wall-disruption. This review provides a comprehensive survey on the necessity of wall-disruption, the impact of wall-disruption on the release and digestion of nutrients, and wall-disruption techniques in industrial production. Wall-disruption appears effective in releasing and digesting nutrients and exploiting bee pollen's bioactivities. Finally, the review underscores the need for future studies to elucidate the mechanisms of beneficial effects. This paper will likely help us gain better insight into bee pollen to develop further functional foods, personalized nutraceuticals, cosmetics products, and medicine.

Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma.

Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

Chemometrics-based Chemical Analysis of Myrrh and Its Vinegar-processed Products by UPLC-MS/MS.

Myrrh is widely used in clinical practice but accompanied by obvious toxicity. According to traditional Chinese medicines theory, processing with vinegar can effectively reduce its toxicity. However, the detoxification processing technology of Myrrh and the corresponding mechanism have been unclear. The objective of this study is to systematically analyze the variation in chemical composition of raw Myrrh and its processed products using UPLC-Q-TOF-MS/MS coupled with chemometrics. A total of 75 compounds including 56 sesquiterpenoids, 2 diterpenoids, 15 triterpenoids and 2 other types were identified. Raw Myrrh and its processed products were divided into two major groups, and 14 chemical markers were selected out by principal component analysis and partial least square discriminant analysis. Additionally, the exact content of 5 representative chemical markers was determined to be significantly reduced after vinegar-processing by UPLC-QQQ-MS/MS. Moreover, multivariate statistical analysis and the quantitative results comprehensively indicated that the optimized processing method was processing at a ratio of 200 : 5 (Myrrh:vinegar). This research provides not only a reliable foundation for the study of Myrrh, but also a scientific reference for clinical use of this herb.

Electromyographic biofeedback therapy for improving limb function after stroke: A systematic review and meta-analysis.

BACKGROUND: Upper and lower limb impairment is common after stroke. Electromyographic biofeedback therapy is a non-invasive treatment, and its effectiveness in functional rehabilitation of the limb after stroke still remains uncertain. OBJECTIVE: The objective of this study was to evaluate whether electromyographic biofeedback can improve upper and lower limb dysfunction in stroke patients. METHODS: PubMed, Embase, Cochrane Library, and Physiotherapy Evidence Database (PEDro) were searched from inception to 1st May 2022. Inclusion criteria were randomized controlled clinical trials of electromyographic biofeedback therapy interventions reporting changes in upper and lower limb function in post-stroke patients. Data were extracted by two independent reviewers and pooled in random-effects models using Review manager (RevMan) software. RESULTS: Our analyses included 10 studies enrolling a total of 303 participants. Electromyographic biofeedback therapy can effectively improve limb function after stroke (standardized mean difference [SMD], 0.44; 95% confidence interval [CI], 0.12-0.77; P = 0.008) and in subgroup analyses, the effect sizes of short-term effect (SMD, 0.33; 95% CI, 0.02-0.64; P = 0.04) was significant, but the long-term was not (SMD, 0.61; 95% CI, -0.11-1.33; P = 0.10). In addition, Electromyographic biofeedback therapy can improve the active range of motion of shoulder (SMD, 1.49; 95% CI, 2.22; P<0.0001) and wrist joints (SMD, 0.77; 95% CI, 0.13-1.42; P = 0.02) after stroke. CONCLUSION: In this meta-analysis, electromyographic biofeedback therapy intervention can improve upper and lower limb function in patients with stroke. Short-term (less than one month) improvement after electromyographic biofeedback therapy was supported, while evidence for long-term (more than one month) benefits was lacking. Range of motion in the glenohumeral and wrist joints were improved. Stronger evidence for individualized parameters, such as optimal treatment parameters and intervention period, is needed in the future. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/display_record.php?recordID=267596], identifier [CRD42022354363].

Chiropractic effects on stride parameters and heart rate during exercise in sport horses.

BACKGROUND: Equine veterinarians performing chiropractic treatments are frequently asked to evaluate and treat sound horses to improve their performance and address pain associated with the axial skeleton. Studies describing the effects and mechanisms of chiropractic treatments in horses without overt lameness are scarce. OBJECTIVES: This study aimed to evaluate the effect of chiropractic treatments on stride rate, length, symmetry, heart rate and rider-perceived quality of the ridden work in sport horses. STUDY DESIGN: A blind randomised controlled trial with crossover design. METHODS: Thirty-eight horses ridden in the hunter-jumper discipline were enrolled. Exercise tests were recorded before and after chiropractic or sham treatment while horses were wearing a fitness tracker. Stride length, rate and symmetry, heart rate and the perceived quality of the ridden work were compared. RESULTS: There was a difference in the qualitative assessment of the ridden work by riders between treatments (odds ratio 33.8, 95% CI [4.68, 458.71], p < 0.01). Stride length, rate, symmetry and heart rate were not different between treatments. MAIN LIMITATIONS: The quantitative outcomes measured may not be sensitive enough to detect changes that improve the ridden work. Terrain, weather and rider were not standard across horses making small changes difficult to detect. CONCLUSIONS: Riders participating in a blind randomised controlled trial perceived a positive effect of chiropractic treatments on the quality of the ridden work. There were no differences in stride length, stride rate, stride symmetry or heart rate. The mechanisms, indications and potential benefits of chiropractic treatments in horses need further study.

HISTORIAL: A los veterinarios de equinos que realizan tratamientos quiroprácticos, se les pide frecuentemente evaluar y tratar caballos que están sanos para mejorar su desempeño y tratar el dolor asociado con el esqueleto axial. Estudios que describen los efectos y mecanismos de los tratamientos quiropráctico en caballos sin cojeras aparentes, son pocos. OBJETIVOS: Este estudio tiene por objetivo evaluar el efecto de los tratamientos quiroprácticos sobre frecuencia, largo y simetría de la zancada, la frecuencia cardiaca y la calidad del trabajo montado percibida por el jinete en caballos de deporte. DISEÑO DEL ESTUDIO: Prueba aleatoria cegada controlada con diseño cruzado. MÉTODOS: Se enrolaron 38 caballos montados en la disciplina de caza-salto. Pruebas de ejercicio fueron anotadas antes y después de tratamientos quiropráctico reales o simulados mientras los caballos llevaban un monitor físico. Se compararon el largo, frecuencia y simetría de la zancada, frecuencia cardiaca y calidad del trabajo montado percibida por el jinete. RESULTADOS: Se encontró una diferencia en la evaluación cualitativa del trabajo montado por los jinetes entre los tratamientos (odds ratio 33.8, 95% CI [4.68, 458.71], p < 0.01). Largo, frecuencia y simetría de zancada y frecuencia cardiacas no difirieron entre tratamientos. LIMITACIONES PRINCIPALES: Los resultados cuantitativos medidos, pueden no ser lo suficientemente sensibles para detectar cambios que mejoran el trabajo montado. El terreno, tiempo y jinete no fueron estandarizados a través de los caballos, lo que hizo que cambios pequeños fuesen difíciles de detectar. CONCLUSIONES: Los jinetes que participaron en una prueba aleatoria cegada controlada, percibieron un efecto positivo de los tratamientos quiroprácticos sobre la calidad del trabajo montado. No hubo diferencia en largo de zancada, frecuencia de zancada, simetría de zancada o frecuencia cardiaca. Los mecanismos, indicaciones y beneficios potenciales de los tratamientos quiroprácticos en caballos necesitan ser estudiados mas.

Exposure risk to rural Residents: Insights into particulate and gas phase pesticides in the Indoor-Outdoor nexus.

Rural residents are exposed to both particulate and gaseous pesticides in the indoor-outdoor nexus in their daily routine. However, previous personal exposure assessment mostly focuses on single aspects of the exposure, such as indoor or gaseous exposure, leading to severe cognition bias to evaluate the exposure risks. In this study, residential dust and silicone wristbands (including stationary and personal wearing ones) were used to screen pesticides in different phases and unfold the hidden characteristics of personal exposure via indoor-outdoor nexus in intensive agricultural area. Mento-Carlo Simulation was performed to assess the probabilistic exposure risk by transforming adsorbed pesticides from wristbands into air concentration, which explores a new approach to integrate particulate (dust) and gaseous (silicone wristbands) pesticide exposures in indoor and outdoor environment. The results showed that particulate pesticides were more concentrated in indoor, whereas significantly higher concentrations were detected in stationary outdoor wristbands (p < 0.05). Carbendazim and chlorpyrifos were the most frequently detected pesticides in dust and stationary wristbands. Higher pesticide concentration was found in personal wristbands worn by farmers, with the maximum value of 2048 ng g-1 for difenoconazole. Based on the probabilistic risk assessment, around 7.1 % of farmers and 2.6 % of bystanders in local populations were potentially suffering from chronic health issues. One third of pesticide exposures originated mainly from occupational sources while the rest derived from remoting dissipation. Unexpectedly, 43 % of bystanders suffered the same levels of exposure as farmers under the co-existence of occupational and non-occupational exposures. Differed compositions of pesticides were found between environmental samples and personal pesticide exposure patterns, highlighting the need for holistic personal exposure measurements.

Vision Transformer-Based Multilabel Survival Prediction for Oropharynx Cancer After Radiation Therapy.

PURPOSE: A reliable and comprehensive cancer prognosis model for oropharyngeal cancer (OPC) could better assist in personalizing treatment. In this work, we developed a vision transformer-based (ViT-based) multilabel model with multimodal input to learn complementary information from available pretreatment data and predict multiple associated endpoints for radiation therapy for patients with OPC. METHODS AND MATERIALS: A publicly available data set of 512 patients with OPC was used for both model training and evaluation. Planning computed tomography images, primary gross tumor volume masks, and 16 clinical variables representing patient demographics, diagnosis, and treatment were used as inputs. To extract deep image features with global attention, we used a ViT module. Clinical variables were concatenated with the learned image features and fed into fully connected layers to incorporate cross-modality features. To learn the mapping between the features and correlated survival outcomes, including overall survival, local failure-free survival, regional failure-free survival, and distant failure-free survival, we employed 4 multitask logistic regression layers. The proposed model was optimized by combining the multitask logistic regression negative-log likelihood losses of different prediction targets. RESULTS: We employed the C-index and area under the curve metrics to assess the performance of our model for time-to-event prediction and time-specific binary prediction, respectively. Our proposed model outperformed corresponding single-modality and single-label models on all prediction labels, achieving C-indices of 0.773, 0.765, 0.776, and 0.773 for overall survival, local failure-free survival, regional failure-free survival, and distant failure-free survival, respectively. The area under the curve values ranged between 0.799 and 0.844 for different tasks at different time points. Using the medians of predicted risks as the thresholds to identify high-risk and low-risk patient groups, we performed the log-rank test, the results of which showed significantly larger separations in different event-free survivals. CONCLUSION: We developed the first model capable of predicting multiple labels for OPC simultaneously. Our model demonstrated better prognostic ability for all the prediction targets compared with corresponding single-modality models and single-label models.

Targeted metabolomics revealed the mechanisms underlying the role of Liansu capsule in ameliorating functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear. AIM OF THE STUDY: To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms. MATERIALS AND METHODS: Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1ß, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD. RESULTS: The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1ß, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5. CONCLUSION: Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD.

ß-asarone improves cognitive impairment and alleviates autophagy in mice with vascular dementia via the cAMP/PKA/CREB pathway.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease. ß-asarone, a major component of Acorus tatarinowii Schott, is important in neurodegenerative and neurovascular diseases. Studies have confirmed that ß-asarone can mitigate autophagy and reduce damage in hypoxic cells. We also reported that ß-asarone improves learning and memory. This study further clarifies whether ß-asarone attenuates cerebral ischaemic injury by acting through the cAMP/PKA/CREB pathway in VD model mice. METHODS: Here, genes and potential pathways that may be targeted by ß-asarone for the treatment of transient cerebral ischaemia (TCI) and cognitive impairment (CI) were obtained using network pharmacology. The two-vessel occlusion method was used to establish the VD model. The Morris water maze test was used to evaluate the effects on memory. Then, the protein levels of mitofusin-2 (Mfn2), brain-derived neurotrophic factor (BDNF), optic atrophy 1 (OPA1), cyclic adenosine monophosphate (cAMP), myelin basic protein (MBP), matrix metalloproteinase-9 (MMP9) and neuron specific enolase (NSE) were determined by ELISA. The levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were measured using commercial kits. Then, qRT-PCR was employed to investigate the expression of the candidate genes screened from the protein-protein interaction (PPI) network. Furthermore, the expression of the autophagy-related proteins Beclin-1, (microtubule-associated protein light chain 3) LC3, p62, postsynaptic density protein 95 (PSD95), protein kinase A (PKA), pPKA, cyclic-AMP response binding protein (CREB), and pCREB was determined by western blotting. The expression of autophagy-related proteins, PSD95 and translocase of outer mitochondrial membrane 20 (TOM20) was determined by immunofluorescence analyses. RESULTS: The network pharmacological analysis showed 234 targets related to ß-asarone, 1,118 genes related to TCI and 2,039 genes associated with CI. Our results confirm that ß-asarone treatment not only alleviated brain damage in the VD model by improving mitochondrial and synaptic function, reducing neuronal injury and upregulating the expression of antioxidants but also effectively improved the cognitive behaviour of VD model mice. Moreover, ß-asarone downregulated VD-induced RELA and CCND1 mRNA expression. In addition, we validated that ß-asarone increased the phosphorylation of PKA and CREB and upregulated cAMP protein expression. The results showed that the cAMP/PKA/CREB signalling pathway was upregulated. Moreover, ß-asarone administration decreased the protein expression levels of Beclin-1 and LC3 and increased the expression levels of p62 in VD model mice. CONCLUSIONS: ß-asarone inhibits Beclin-1-dependent autophagy and upregulates the cAMP/PKA/CREB signalling pathway to attenuate mitochondrial and synaptic damage from cerebral ischaemia and improve learning and cognitive abilities in VD model mice.

UGT89AC1-mediated quercetin glucosylation is induced upon herbivore damage and enhances Camellia sinensis resistance to insect feeding.

Quercetin is a key flavonol in tea plants (Camellia sinensis (L.) O. Kuntze) with various health benefits, and it often occurs in the form of glucosides. The roles of quercetin and its glucosylated forms in plant defense are generally not well-studied, and remain unknown in the defense of tea. Here, we found higher contents of quercetin glucosides and a decline of the aglucone upon Ectropis grisescens (E. grisescens) infestation of tea. Nine UGTs were strongly induced, among which UGT89AC1 exhibited the highest activity toward quercetin in vitro and in vivo. The mass of E. grisescens larvae that fed on plants with repressed UGT89AC1 or varieties with lower levels of UGT89AC1 was significantly lower than that of larvae fed on controls. Artificial diet supplemented with quercetin glucoside also reduced the larval growth rate, whereas artificial diet supplemented with free quercetin had no significant effect on larval growth. UGT89AC1 was located in both the cytoplasm and nucleus, and its expression was modulated by JA, JA-ILE, and MeJA. These findings demonstrate that quercetin glucosylation serves a defensive role in tea against herbivory. Our results also provide novel insights into the ecological relevance of flavonoid glycosides under biotic stress in plants.

Impact of miR-519d on the Biological Activity of Non-Small Cell Lung Cancer Cells and Its Mechanism.

Objective: This study aimed to investigate the impact of miR-519d on the biological activity of non-small cell lung cancer (NSCLC) cells and elucidate its underlying mechanism. Methods: An experimental study design was adopted, and a cell culture-based study was conducted. We obtained non-small cell lung cancer cell lines from the ATCC cell bank and categorized them into three groups: the miR group, the NSCLC group, and the Negative control group. Various methods, including flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), Transwell assays, Western blotting, and the Cell Counting Kit-8 (CCK-8) assay, were employed to assess miR-519d expression, apoptosis, proliferation, migration, and nuclear factor-kappa B (NF-KB) p65 protein content, thus exploring the impact of miR-519d on the biological activity of NSCLC cells. Results: In the miR group, we observed the highest expression level of miR-519d in NSCLC cells. Furthermore, the miR group exhibited the greatest number of apoptotic cells and the highest apoptosis rate (P < .05). Notably, the Transwell assay revealed reduced migration of NSCLC cells in the miR group, while the NSCLC cells in the control group exhibited more migratory activity. The cell counts of NSCLC cells also significantly decreased in the miR group, with migration comparable to the Negative control group (P > .05). Western blot analysis indicated that NF-KB p65 protein expression was highest in the Negative control group but significantly reduced in the miR group (all P < .05). Conclusions: miR-519d is downregulated in NSCLC cells. Elevating the expression of miR-519d inhibits various biological activities of lung cancer cells, including migration and proliferation. The downregulation of NF-KB p65 likely mediates this inhibition.