BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Interactions between Beta-Amyloid and Pericytes in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aß) that make up Aß plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aß through various receptors, and Aß acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aß1-40 and Aß1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aß from the brain interstitial fluid. The aggravated deposition of Aß further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aß is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aß, as well as current and further strategies for preventing or treating AD targeting pericytes.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Demographics and Clinical Characteristics of Patients with Neurocysticercosis: A Retrospective Study from Dali, China.

Background: Neurocysticercosis (NCC), a predominant parasitic disease that affects the central nervous system and presents with diverse clinical manifestations, is a major contributor to acquired epilepsy worldwide, particularly in low-, middle-, and upper middle-income nations, such as China. In China, the Yunnan Province bears a significant burden of this disease. Objective: To describe the demographic, clinical, and radiological features as well as serum and cerebrospinal fluid antibodies to cysticercus in patients with NCC from Dali, Yunnan Province, China. Materials and Methods: This retrospective study included patients who were diagnosed with NCC at The First Affiliated Hospital of Dali University between January 2018 and May 2023 and were residing in Dali, Yunnan Province, China. Results: A total of 552 patients with NCC were included, of which 33.3% belonged to Bai ethnicity. The clinical presentation of NCC exhibited variability that was influenced by factors such as the number, location, and stage of the parasites. Epilepsy/seizure (49.9%) was the most prevalent symptom, with higher occurrence in the degenerative stage of cysts (P < 0.001). Compared with other locations, cysticerci located in the brain parenchyma are more likely to lead to seizures/epilepsy (OR = 17.45, 95% CI: 7.96-38.25) and headaches (OR = 3.02, 95% CI: 1.23-7.41). Seizures/epilepsy are more likely in patients with cysts in the vesicular (OR = 2.71, 95% CI: 1.12-6.61) and degenerative (OR = 102.38, 95% CI: 28.36-369.60) stages than those in the calcified stage. Seizures was not dependent on the number of lesions. All NCC patients underwent anthelminthic therapy, with the majority receiving albendazole (79.7%). Conclusion: This study provides valuable clinical insights into NCC patients in Dali and underscores the significance of NCC as a leading preventable cause of epilepsy.

7,8,3'-Trihydroxyflavone prevents doxorubicin-induced cardiotoxicity and mitochondrial dysfunction via activating Akt signaling pathway in H9c2 cells.

Clinical application of the widely used chemotherapeutic agent, doxorubicin (DOX), is limited by its cardiotoxicity. Mitochondrial dysfunction has been revealed as a crucial factor in DOX-induced cardiotoxicity. 7,8,3'-Trihydroxyflavone (THF) is a mimetic brain-derived neurotrophic factor with neuroprotective effects. However, the potential effects of THF on DOX-induced cardiomyocyte damage and mitochondrial disorders remain unclear. H9c2 cardiomyoblasts were exposed to DOX and/or THF at different concentrations. Cardiomyocyte injury was evaluated using lactate dehydrogenase (LDH) assay and Live/Dead cytotoxicity kit. Meanwhile, mitochondrial membrane potential (MMP), morphology, mitochondrial reactive oxygen species (mito-ROS) production, and the oxygen consumption rate of cardiomyocytes were measured. The protein levels of key mitochondria-related factors such as adenosine monophosphate-activated protein kinase (AMPK), mitofusin 2 (Mfn2), dynamin-related protein 1 (Drp1), and optic atrophy protein 1 (OPA1) were examined. We found that THF reduced LDH content and death ratio of DOX-treated cardiomyocytes in a concentration-dependent manner, while increasing MMP without significantly affecting the routine and maximum capacity of mitochondrial respiration. Mechanistically, THF increased the activity of Akt and protein levels of Mfn2 and heme oxygenase 1 (HO-1). Moreover, inhibition of Akt reversed the protective role of THF, increased mito-ROS levels, and repressed Mfn2 and HO-1 expression. Therefore, we conclude, THF relieves DOX-induced cardiotoxicity and improves mitochondrial function by activating Akt-mediated Mfn2 and HO-1 pathways. This finding provides promising therapeutic insights for DOX-induced cardiac dysfunction.

Efficient genome editing in cotton using the virus-mediated CRISPR/Cas9 and grafting system.

KEY MESSAGE: The extensive application of CRISPR in cotton was limited due to the labor-intensive transformation process. Thus, we here established a convenient method of CRISPR in cotton by CLCrV-mediated sgRNA delivery.

BDNF mimetic 7,8-dihydroxyflavone rescues rotenone-induced cytotoxicity in cardiomyocytes by ameliorating mitochondrial dysfunction.

The relationship between mitochondrial dysfunction and cardiovascular disease pathogenesis is well recognized. 7,8-Dihydroxyflavone (7,8-DHF), a mimetic of brain-derived neurotrophic factor, inhibits mitochondrial impairments and improves cardiac function. However, the regulatory role of 7,8-DHF in the mitochondrial function of cardiomyocytes is not fully understood. To investigate the potential mito-protective effects of 7,8-DHF in cardiomyocytes, we treated H9c2 or HL-1 cells with the mitochondrial respiratory complex I inhibitor rotenone (Rot) as an in vitro model of mitochondrial dysfunction. We found that 7,8-DHF effectively eliminated various concentrations of Rot-induced cell death and reduced lactate dehydrogenase release. 7,8-DHF significantly improved mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species. Moreover, 7,8-DHF decreased routine and leak respiration, restored protein levels of mitochondrial complex I-IV, and increased ATP production in Rot-treated H9c2 cells. The protective role of 7,8-DHF in Rot-induced damage was validated in HL-1 cells. Nuclear phosphorylation protein expression of signal transducer and activator of transcription 3 (STAT3) was significantly increased by 7,8-DHF. The present study suggests that 7,8-DHF rescues Rot-induced cytotoxicity by inhibiting mitochondrial dysfunction and promoting nuclear translocation of p-STAT3 in cardiomyocytes, thus nominating 7,8-DHF as a new pharmacological candidate agent against mitochondrial dysfunction in cardiac diseases.

Malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.

Unicentric Castleman disease was misdiagnosed as pancreatic mass: A case report.

BACKGROUND: Castleman's disease (CD) is a lymphatic proliferative disorder of unknown cause and is rarely seen clinically. It has been divided into unicentric and multicentric types. Unicentric CD (UCD) occurs as a solitary enlarged mass and mediastinal lymph nodes are the most common site. Surgical excision has proven to be curative for UCD. Multicentric CD (MCD) appears as a systemic disease with peripheral lymphadenopathy. MCD had a poor response to surgery and monoclonal antibodies with rituximab have become a research hotspot. CASE SUMMARY: A 44-year-old woman presented with a pancreatic mass during routine physical examination. She had no obvious symptoms, such as fever, abdominal pain, abdominal distension, or jaundice. Ultrasound examination indicated a hypoechoic mass between the body of the pancreas, left lobe of the liver and stomach. It had a clear boundary, irregular shape, uneven echo, and no obvious blood flow signals. To clarify the diagnosis, contrast-enhanced ultrasound examination was performed, which showed a benign pancreatic lesion. Neuroendocrine or solid pseudopapillary tumor was a possible diagnosis. The patient underwent further contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging, which were suggestive of solid pseudopapillary tumor or neuroendocrine tumor. All the examinations failed to give a definitive diagnosis, and the patient underwent surgery. The final pathological and immunohistochemical results showed that the mass was CD. CONCLUSION: This case highlights when lymphadenopathy is encountered clinically, CD should be considered and a biopsy should be performed.

Isolation and structure elucidation of two new cassane derivatives from the seed kernels of Caesalpinia sinensis.

Two new cassane-type derivatives (1-2), together with three known compounds (3-5), were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2, possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia. All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1-5 could inhibit production of NO at the concentration of 50 µM.

A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.

The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.

An unusual huge thymoma composed of sclerosing thymoma and type AB thymoma: A case report.

RATIONALE: Sclerosing thymoma (ST) is quite a rare disease, as denoted in previous literature. Less than 20 cases of ST have been reported to date. However, the combined thymoma, composed of both type AB thymoma and ST, has never been described before. PATIENT CONCERNS: The subject, a 49-year-old woman, came in with the chief complaint of cough for 10 days. DIAGNOSES: Both the contrast-enhanced computed tomography scan and the ultrasonography showed a huge mass located in the right thoracic cavity with inhomogeneous contrast accompanied by the invasion of the pericardium and pleura. Subsequently, computed tomography-guided core-needle biopsy revealed type B2 thymoma, and type AB thymoma could not be excluded. Based on postsurgical histopathology and immunohistochemical finding, this tumor was given the final diagnosis of ST and type AB thymoma. INTERVENTIONS: After 6 months of adjuvant chemotherapy and local radiotherapy, total thymectomy was performed. OUTCOMES: The patient has been duly followed up for 1 year without any tumor recurrence. LESSONS: ST is a very rare mediastinal neoplasm. Moreover, ST in combination with AB thymoma and affecting a large area, is unprecedented. Whether radiotherapy and chemotherapy have a certain effect on ST requires further investigation. In addition, due to the unclear recurrence rate of ST, long-term follow-up evaluation seems necessary.

A rational design of layered metal-organic framework towards high-performance adsorption of hazardous organic dye.

Water pollution originating from organic dyes is endangering the survival and development of society; however, adsorbents with high capacity (>5000 mg g-1) for the fast removal (≤30 min) of Congo Red (CR) in aqueous solution have been not reported to date. In the present work, an acid-base stably layered MOF, [Cd(H2L)(BS)2]n·2nH2O (L-MOF-1, H2L = N1,N2-bis(pyridin-3-ylmethyl)ethane-1,2-diamine, BS = benzenesulfonate), was hydrothermally prepared. L-MOF-1 exhibited high-performance adsorption of CR in aqueous solution at room temperature. The experimental adsorption capacity of the L-MOF-1 adsorbent towards CR reached up to about 12 000 mg g-1 in 20 min in the pH range of 2.2-4.7, which is the best adsorbent with the highest capacity and fastest adsorption of CR to date. The spontaneous adsorption process can be described by the pseudo-second-order kinetic and Langmuir isotherm models. Meanwhile, the L-MOF-1 absorbent possessed a highly positive zeta potential in acid condition (even at pH = 2.2, zeta potential = 36.2 mV). Its good adsorption performance mainly originates from its strong electrostatic attraction with CR in acidic condition, together with diverse hydrogen bonds and ππ stacking interactions. Furthermore, the L-MOF-1 absorbent exhibited good selectivity and could be reused five times through simply washing, where its adsorption efficiency was hardly affected. Therefore, L-MOF-1 is a potential absorbent for effectively removing CR from dye wastewater.

[Multiple subcutaneous nodules for 46 days in an infant aged 66 days].

A boy, aged 66 days, was admitted to the hospital due to subcutaneous nodules for 46 days and abdominal distension for 10 days. The main clinical manifestations were loss of adipose tissue, subcutaneous nodules, insulin-resistant diabetes, hypertriglyceridemia, and hepatic steatosis. The boy was diagnosed with congenital generalized lipodystrophy type 1 (CGL1). His condition was improved after administration of middle-chain fatty acid formula milk and insulin injection or oral metformin. Gene testing revealed a homozygous mutation, c.646A>T, in the AGPAT2 gene, and both his parents were carriers of this mutation. This case of CGL1 has the youngest age of onset ever reported in China and multiple subcutaneous nodules as the initial symptom.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study.

BACKGROUND: Multiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA. AIM: To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson's disease (PD) patients and healthy controls. METHODS: A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD. RESULTS: Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively). CONCLUSION: Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Identification of NHXs in Gossypium species and the positive role of GhNHX1 in salt tolerance.

BACKGROUND: Plant Na+/H+ antiporters (NHXs) are membrane-localized proteins that maintain cellular Na+/K+ and pH homeostasis. Considerable evidence highlighted the critical roles of NHX family in plant development and salt response; however, NHXs in cotton are rarely studied. RESULTS: The comprehensive and systematic comparative study of NHXs in three Gossypium species was performed. We identified 12, 12, and 23 putative NHX proteins from G. arboreum, G. raimondii, and G. hirsutum, respectively. Phylogenetic study revealed that repeated polyploidization of Gossypium spp. contributed to the expansion of NHX family. Gene structure analysis showed that cotton NHXs contain many introns, which will lead to alternative splicing and help plants to adapt to high salt concentrations in soil. The expression changes of NHXs indicate the possible differences in the roles of distinct NHXs in salt response. GhNHX1 was proved to be located in the vacuolar system and intensively induced by salt stress in cotton. Silencing of GhNHX1 resulted in enhanced sensitivity of cotton seedlings to high salt concentrations, which suggests that GhNHX1 positively regulates cotton tolerance to salt stress. CONCLUSION: We characterized the gene structure, phylogenetic relationship, chromosomal location, and expression pattern of NHX genes from G. arboreum, G. raimondii, and G. hirsutum. Our findings indicated that the cotton NHX genes are regulated meticulously and differently at the transcription level with possible alternative splicing. The tolerance of plants to salt stress may rely on the expression level of a particular NHX, rather than the number of NHXs in the genome. This study could provide significant insights into the function of plant NHXs, as well as propose promising candidate genes for breeding salt-resistant cotton cultivars.

An improved method for the preparation of Ginsenoside Rg5 from ginseng fibrous root powder.

Ginsenoside-Rg5, which is derived from high temperature-processed ginseng, exhibits beneficial health effects. In the present study, ginsenoside-Rg5 was directly and rapidly prepared through the extraction of ginseng fibrous root powder (GFRP) at atmospheric pressure. The results showed that the highest extraction yield (3.79%) was obtained under optimal conditions (extraction temperature of 85 °C, acid concentration of 0.06 mol/L, sample to solvent ratio of 1:55 g/mL and ethanol concentration of 95% after 4 h). The current method integrates the extraction of original saponins and the modification of the saponins to rare ginsenosides Rg5, which was more simpler operation, more milder preparation condition and more efficient.

Food Frequency Questionnaire for Chinese Children Aged 12-17 Years: Validity and Reliability.

OBJECTIVE: The primary objective of this study was to examine the validity and reliability of a semi-quantitative food frequency questionnaire (FFQ) among Chinese children aged 12-17 years. METHODS: A semi-quantitative 72-food item FFQ was developed for children aged 12-17 years. The reliability and validity of this FFQ were evaluated against 24-h dietary recalls (24 h DRs) to measure the consumption of foods and nutrients. We administered two FFQs and three DRs to children (N = 160) over a period of 1 month to evaluate the reliability and validity. Reliability was examined by quartile agreement and intraclass correlation coefficients (ICCs), and validity was examined by quartile agreement, Bland-Altman plots and correlation with DRs. RESULTS: For reliability, the ICCs between the two FFQs ranged from 0.21 to 0.76 for foods and nutrients, and the quartile agreement ranged from 70.0% to 95.0% in the same or adjacent quartiles. Spearman's correlation coefficients of foods and nutrients between the second FFQ and the 24 h DRs ranged from -0.04 to 0.59. The Bland-Altman plots demonstrated good agreement across the range of intakes among nutrients. The quartile agreement ranged from 50.0% to 100.0%, with infrequent misclassification. CONCLUSION: The FFQ assessment of dietary intakes demonstrated acceptable relative validity and high reproducibility for Chinese children aged 12-17 years.