An exploration on the machine-learning-based stroke prediction model.

Introduction: With the rapid development of artificial intelligence technology, machine learning algorithms have been widely applied at various stages of stroke diagnosis, treatment, and prognosis, demonstrating significant potential. A correlation between stroke and cytokine levels in the human body has recently been reported. Our study aimed to establish machine-learning models based on cytokine features to enhance the decision-making capabilities of clinical physicians. Methods: This study recruited 2346 stroke patients and 2128 healthy control subjects from Chongqing University Central Hospital. A predictive model was established through clinical experiments and collection of clinical laboratory tests and demographic variables at admission. Three classification algorithms, namely Random Forest, Gradient Boosting, and Support Vector Machine, were employed. The models were evaluated using methods such as ROC curves, AUC values, and calibration curves. Results: Through univariate feature selection, we selected 14 features and constructed three machine-learning models: Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting Machine (GBM). Our results indicated that in the training set, the RF model outperformed the GBM and SVM models in terms of both the AUC value and sensitivity. We ranked the features using the RF algorithm, and the results showed that IL-6, IL-5, IL-10, and IL-2 had high importance scores and ranked at the top. In the test set, the stroke model demonstrated a good generalization ability, as evidenced by the ROC curve, confusion matrix, and calibration curve, confirming its reliability as a predictive model for stroke. Discussion: We focused on utilizing cytokines as features to establish stroke prediction models. Analyses of the ROC curve, confusion matrix, and calibration curve of the test set demonstrated that our models exhibited a strong generalization ability, which could be applied in stroke prediction.

Perceptions of Chinese women with a history of gestational diabetes regarding health behaviors and related factors: a directed qualitative content analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse outcomes in both mothers and their children. After delivery, women who experience GDM are also at higher risk of both subsequent GDM and type 2 diabetes mellitus (T2DM) than those who do not. Therefore, healthcare providers and public health practitioners need to develop targeted and effective interventions for GDM. In this study, we aimed to explore the perceptions regarding health behaviors and related factors during the inter-pregnancy period among Chinese women with a history of GDM through the lens of the theory of planned behavior (TPB). METHODS: Between December 2021 and September 2022, 16 pregnant Chinese women with a history of GDM were purposively recruited from a tertiary maternity hospital in Shanghai for face-to-face semi-structured interviews. They were asked questions regarding their health behaviors and related factors. The transcribed data were analyzed using a directed qualitative content analysis method based on the theory of TPB. RESULTS: The health-related behaviors of the women varied substantially. We identified five domains that influenced women's behaviors according to TPB constructs and based on the data collected: behavioral attitude (perceived benefits of healthy behaviors and the relationship between experience and attitude towards the oral glucose tolerance testing); subjective norms (influences of significant others and traditional cultural beliefs); perceived behavior control (knowledge of the disease, multiple-role conflict, the impact of COVID-19, an unfriendly external environment and difficulty adhering to healthy diets), incentive mechanisms (self-reward and external incentives); preferences of professional and institutional support (making full use of social media platform and providing continuous health management). CONCLUSIONS: The health-related behaviors of women with a history of GDM were found to be affected by multiple factors. Healthcare professionals are recommended to provide women with sufficient information regarding the disease and to take advantage of the power of the family and other social support networks to improve women's subjective norms and to promote the adoption of a healthy lifestyle.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Development of rapid nucleic acid testing techniques for common respiratory infectious diseases in the Chinese population.

Background: Most respiratory viruses can cause serious lower respiratory diseases at any age. Therefore, timely and accurate identification of respiratory viruses has become even more important. This study focused on the development of rapid nucleic acid testing techniques for common respiratory infectious diseases in the Chinese population. Methods: Multiplex fluorescent quantitative polymerase chain reaction (PCR) assays were developed and validated for the detection of respiratory pathogens including the novel coronavirus (SARS-CoV-2), influenza A virus (FluA), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). Results: The assays demonstrated high specificity and sensitivity, allowing for the simultaneous detection of multiple pathogens in a single reaction. These techniques offer a rapid and reliable method for screening, diagnosis, and monitoring of respiratory pathogens. Conclusion: The implementation of these techniques might contribute to effective control and prevention measures, leading to improved patient care and public health outcomes in China. Further research and validation are needed to optimize and expand the application of these techniques to a wider range of respiratory pathogens and to enhance their utility in clinical and public health settings.

Elucidating the unexpected importance of intermediate-volatility organic compounds (IVOCs) from refueling procedure.

Evaporative emissions release organic compounds comparable to gasoline exhaust in China. However, the measurement of intermediate volatility organic compounds (IVOCs) is lacking in studies focusing on gasoline evaporation. This study sampled organics from a real-world refueling procedure and analyzed the organic compounds using comprehensive two-dimensional gas chromatography coupled with a mass spectrometer (GC×GC-MS). The non-target analysis detected and quantified 279 organics containing 93 volatile organic compounds (VOCs, 64.9 ± 7.4 % in mass concentration), 182 IVOCs (34.9 ± 7.4 %), and 4 semivolatile organic compounds (SVOCs, 0.2 %). The refueling emission profile was distinct from that of gasoline exhaust. The b-alkanes in the B12 volatility bin are the most abundant IVOC species (1.9 ± 1.4 µg m-3) in refueling. A non-negligible contribution of 17.5 % to the ozone formation potential (OFP) from IVOCs was found. Although IVOCs are less in concentration, secondary organic aerosol potential (SOAP) from IVOCs (58.1 %) even exceeds SOAP from VOCs (41.6 %), mainly from b-alkane in the IVOC range. At the molecular level, the proportion of cyclic compounds in SOAP (12.1 %) indeed goes above its mass concentration (3.1 %), mainly contributed by cyclohexanes and cycloheptanes. As a result, the concentrations and SOAP of cyclic compounds (>50 %) could be overestimated in previous studies. Our study found an unexpected contribution of IVOCs from refueling procedures to both ozone and SOA formation, providing new insights into secondary pollution control policy.

Diagnostic value of contrast-enhanced ultrasound in the diagnosis of papillary thyroid microcarcinoma: A systematic review and meta-analysis.

BACKGROUND: Using meta-analysis to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in the diagnosis of papillary thyroid microcarcinoma (PTMC). METHODS: For this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Web of Science, WanFang Data, VPCS Data, and China National Knowledge Infrastructure electronic databases for diagnostic studies on PTMC by CEUS from January 2013 to November 2022. Data were not available or incomplete such as case reports, nonhuman studies, etc, were excluded. Random-effects meta-analyses were used to evaluate the diagnostic accuracy of CEUS in diagnosing PTMC. The quality of the evidence was assessed with the QUADAS-2 scale. This study is registered on PROSPERO, number CRD42023409417. RESULTS: Of 1064 records identified, 33 were eligible. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS in diagnosing PTMC were 0.84 (95% confidence interval [CI] = 0.83-0.86), 0.82 (95% CI = 0.80-0.83), 3.90 (95% CI = 3.23-4.72), 0.21 (95% CI = 0.18-0.25), and 20.01 (95% CI = 14.97-26.74), respectively, and the area under the summary receiver operating characteristic curve was 0.8930 (the Q index was 0.8239). The Deek funnel plot indicated publication bias (P ˂.01). CONCLUSION: This meta-analysis provides an overview of diagnostic accuracy of CEUS in diagnosing PTMC which indicates CEUS has a good diagnostic value for PTMC. The limitations of this study are publication bias and strong geographical bias.

The effects of Atractylodes macrocephala extract BZEP self-microemulsion based on gut-liver axis HDL/LPS signaling pathway to ameliorate metabolic dysfunction-associated fatty liver disease in rats.

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

Gustatory dysfunction and long COVID in Chinese patients with COVID-19: A 6-month follow-up study.

AIMS: To evaluate long COVID of gustatory dysfunction and the associated risk factors regarding onset and recovery in Chinese patients. METHODS: We conducted a cross-sectional study of patients with SARS-CoV-2 Omicron infection at Changxing Mobile Cabin Hospital in Shanghai, China, from March to May 2022. A prospective follow-up of patients with gustatory dysfunction was conducted at 6 months after discharge. RESULTS: In total, 18.48% (241/1304) reported gustatory dysfunction. The 6-month follow-up response rate was 89.63% (216/241) and 74.02% recovered their taste sense within 1-3 weeks. A total of 20.37% of patients (44/216) presented with long COVID. Symptoms persisted for 12 patients (5.56%) after 6 months. Having multiple taste impairments (OR, 2.364; 95% CI, 1.286-4.348; p = 0.006) was associated with a higher risk of gustatory dysfunction with long COVID. Having received a COVID-19 vaccine booster was positively associated with taste sensation recovery (HR, 1.344; 95% CI, 1.012-1.785; p = 0.041). CONCLUSIONS: About 20.37% of patients with COVID-19 might develop long COVID of gustatory dysfunction and 5.56% with persisting changes in their sense of taste. Most patients recovered taste sensations within 1-3 weeks after COVID-19 symptom onset and receiving a booster shot of the COVID-19 vaccine presented a protective effect on the taste sensation recovery.

Discrimination of untreated and sodium sulphite treated bean sprouts by Fourier transform infrared spectroscopy and chemometrics.

Sprouts of black beans (Phaseolus vulgaris L.), soybeans (Glycine max L.) and mung beans (Vigna radiata L.) are widely consumed foods containing abundant nutrients with biological activities. They are commonly treated with sulphites for the preservation and extension of shelf-life. However, our previous investigation found that immersing the bean sprouts in sulphite might convert the active components into sulphur-containing derivatives, which can affect both the quality and safety of the sprouts. This study explores the use of FTIR in conjunction with chemometric techniques to differentiate between non-immersed (NI) and sodium sulphite immersed (SI) black bean, soybean and mung bean sprouts. A total of 168 batches of raw spectra were obtained from NI and SI-bean sprouts using FTIR spectroscopy. Four pre-processing techniques, three modelling assessment techniques and four model evaluation indices were examined for differences in performance. The results show that the multiplicative scatter correction is the most effective pre-processing method. Among the models, the accuracy rate of the three models was as follows: radial basis function neural network (95%) > convolutional neural network (91%) > random forest (82%). The overall findings indicate that FTIR spectroscopy, in conjunction with appropriate chemometric approaches, has a high potential for rapidly determining the difference between NI and SI-bean sprouts.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

The anti-hyperlipidemia effect of Atractylodes macrocephala Rhizome increased HDL via reverse cholesterol transfer.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Preparation and characterization of vitamin A microcapsules nutrient fortified salt.

Vitamin A, also known as retinol, is a fat-soluble vitamin that plays crucial role in various physiological functions In vivo. However, factors such as light, oxygen, and others may impact the stability of VA. To enhance its stability. This study microencapsulated VA, Gelatin, carboxymethyl cellulose, and salt were mixed in a ratio of 5:1:0.1 as the shell material. Additionally, 12% TG and 3.5% sucrose ester were added with core-shell ratio of 1:8. The experimental results indicated that VA microcapsules exhibited an encapsulation efficiency of 81.12%, after 9 weeks of storage this rate decreased to 75.38%, and the encapsulated VA oil did not exhibit extravasation. The addition of an appropriate amount of salt to the shell material enhanced the mechanical properties of the shell material, compared to the shell material without added salt, the leakage of VA in the salt-added sample decreased by 5.8% for 30 min and 14.5% for 60 min. In vitro release experiments showed that after 3 h of incubation in simulated gastric fluid, the microcapsules had an 18.52% release rate. In simulated intestinal fluid, this increased to 66.58%, indicating strong enteric solubility. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05962-w.

Prenatal Diagnosis of Cerebellar Cortical Dysplasia: Case Report.

This was a study of 12 cerebellar cortical dysplasias (CCDs) fetuses, these cases were characterized by a disorder of cerebellar fissures. Historically, CCD diagnosis was primarily performed using postnatal imaging. Unique to this study was the case series of CCD for prenatal diagnosis using prenatal ultrasound, as well as we found that AXIN1 and FOXC1 mutations may be related to CCD.

Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma.

Therapeutic strategies are the hot-spot issues in treating patients with advanced oral squamous cell carcinoma (OSCC). Mounting studies have proved that triggering ferroptosis is one of the promising targets for OSCC management. In this study, we performed a first attempt to collect the current evidence on the proposed roles of ferroptosis in OSCC through a comprehensive review. Based on clinical data from the relevant studies within this topic, we found that ferroptosis-associated tumor microenvironment, ferroptosis-related genes (FRGs), and ferroptosis-related lncRNAs exhibited a potent prognostic value for OSCC patients. Mechanistically, experimental data revealed that the proliferation and tumorigenesis of OSCC might be associated with the inhibition of cellular ferroptosis through the activation of glutathione peroxidase 4 (GPX4) and adipocyte enhancer-binding protein 1 (AEBP1), suppression of glutathione (GSH) and Period 1 (PER1) expression, and modulation of specific non-coding RNAs (i.e., miR-520d-5p, miR-34c-3p, and miR-125b-5p) and their targeted proteins. Several specific interventions (i.e., Quisinostat, Carnosic acid, hyperbaric oxygen, melatonin, aqueous-soluble sporoderm-removed G. lucidum spore powder, and disulfiram/copper complex) were found to dramatically induce ferroptosis cell death of OSCC via multiple mechanisms. This review highlighted the pivotal role of ferroptosis in the pathogenesis and prognosis of OSCC. Future anticancer therapeutic strategies targeting ferroptosis and its associated molecules might provide a new insight for OSCC treatment.

Circulating immune cell phenotyping is potentially relevant for diabetic retinopathy risk assessment.

BACKGROUND: Inflammation is believed to play a central role in the development of diabetes mellitus and is a common feature of type 2 diabetes mellitus (T2DM). However, the association with diabetic retinopathy (DR) remains a topic of debate. METHODS: This study employed two-sample bidirectional Mendelian randomization (MR) analyses to establish causal associations between immune cell characteristics and DR. Using publicly available GWAS genetic data, we investigated the causal relationship between 731 immune cell characteristics and the risk of DR. A total of four types of immune features, including relative cell (RC), absolute cell (AC), median fluorescence intensities (MFI), and morphological parameters (MP), were included. Sensitivity analysis was conducted to assess the robustness, heterogeneity, and potential horizontal pleiotropy of the results. RESULTS: Thirty-five immune cell phenotypes were correlated with the risk of developing DR among four immune traits (MFI, RC, AC, and MP), and DR resulted in altered expression of twenty-six immune cells. CONCLUSION: We have demonstrated a strong correlation between immune cell traits and DR using a genetic approach. This finding offers valuable insights for early DR prevention and future clinical research and treatment.

Network pharmacology-based research into the mechanism of ferulic acid on acute lung injury through enhancing transepithelial sodium transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferulic acid (FA) has shown potential therapeutic applications in treating lung diseases. However, the underlying mechanisms by which FA ameliorates acute lung injury (ALI) have not been distinctly elucidated. AIM OF THE STUDY: The project aims to observe the therapeutic effects of FA on lipopolysaccharide-induced ALI and to elucidate its specific mechanisms in regulating epithelial sodium channel (ENaC), which majors in alveolar fluid clearance during ALI. MATERIALS AND METHODS: In this study, the possible pathways of FA were determined through network pharmacology analyses. The mechanisms of FA in ALI were verified by in vivo mouse model and in vitro studies, including primary alveolar epithelial type 2 cells and three-dimensional alveolar organoid models. RESULTS: FA ameliorated ALI by improving lung pathological changes, reducing pulmonary edema, and upregulating the α/γ-ENaC expression in C57BL/J male mice. Simultaneously, FA was observed to augment ENaC levels in both three-dimensional alveolar organoid and alveolar epithelial type 2 cells models. Network pharmacology techniques and experimental data from inhibition or knockdown of IkappaB kinase ß (IKKß) proved that FA reduced the phosphorylation of IKKß/nuclear factor-kappaB (NF-κB) and eliminated the lipopolysaccharide-inhibited expression of ENaC, which could be regulated by nuclear protein NF-κB p65 directly. CONCLUSIONS: FA could enhance the expression of ENaC at least in part by inhibiting the IKKß/NF-κB signaling pathway, which may potentially pave the way for promising treatment of ALI.

Plantaginis semen ameliorates diabetic kidney disease via targeting the sphingosine kinase 1/sphingosine-1-phosphate pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field. AIM: This study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models. METHODS: The main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined. RESULTS: A total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV). CONCLUSION: Our results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.

Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.