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1.
Clin Transl Med ; 14(10): e70029, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39350476

ABSTRACT

INTRODUCTION: Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited. OBJECTIVES: To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA. METHODS: The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo. RESULTS: Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (Ggpps) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process . CONCLUSIONS: Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA. KEY POINTS: High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice. Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles. Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.


Subject(s)
Adipose Tissue , Extracellular Vesicles , Obesity , Osteoarthritis , Extracellular Vesicles/metabolism , Animals , Osteoarthritis/metabolism , Osteoarthritis/etiology , Obesity/metabolism , Obesity/complications , Mice , Adipose Tissue/metabolism , Humans , Male , Female , Temporomandibular Joint/metabolism , Temporomandibular Joint/pathology , Temporomandibular Joint Disorders/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Mice, Inbred C57BL , Disease Models, Animal
2.
Article in English | MEDLINE | ID: mdl-39360467

ABSTRACT

BACKGROUND: The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients. METHODS: This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: highpre-highpost, highpre-lowpost, lowpre-highpost and lowpre-lowpost. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models. RESULTS: A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with highpre-highpost, those with highpre-lowpost (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with lowpre-lowpost were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with lowpre-highpost had similar risk of RFS compared to those with highpre-highpost at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05). CONCLUSIONS: Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.

4.
CNS Neurosci Ther ; 30(9): e70067, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39328008

ABSTRACT

AIMS: Neuropathic pain remains a significant unmet medical challenge due to its elusive mechanisms. Recent clinical observations suggest that vitamin D (VitD) holds promise in pain relief, yet its precise mechanism of action is still unclear. This study explores the therapeutical role and potential mechanism of VitD3 in spared nerve injury (SNI)-induced neuropathic pain rat model. METHODS: The analgesic effects and underlying mechanisms of VitD3 were evaluated in SNI and naïve rat models. Mechanical allodynia was assessed using the Von Frey test. Western blotting, immunofluorescence, biochemical assay, and transmission electron microscope (TEM) were employed to investigate the molecular and cellular effects of VitD3. RESULTS: Ferroptosis was observed in the spinal cord following SNI. Intrathecal administration of VitD3, the active form of VitD, activated the vitamin D receptor (VDR), suppressed ferroptosis, and alleviated mechanical nociceptive behaviors. VitD3 treatment preserved spinal GABAergic interneurons, and its neuroprotective effects were eliminated by the ferroptosis inducer RSL3. Additionally, VitD3 mitigated aberrant mitochondrial morphology and oxidative metabolism in the spinal cord. Mechanistically, VitD3 inhibited SNI-induced activation of spinal PKCα/NOX4 signaling. Inhibition of PKCα/NOX4 signaling alleviated mechanical pain hypersensitivity, accompanied by reduced ferroptosis and mitochondrial dysfunction in SNI rats. Conversely, activation of PKCα/NOX4 signaling in naïve rats induced hyperalgesia, ferroptosis, loss of GABAergic interneurons, and mitochondrial dysfunction in the spinal cord, all of which were reversed by VitD3 treatment. CONCLUSIONS: Our findings provide evidence that VitD3 attenuates neuropathic pain by preserving spinal GABAergic interneurons through the suppression of mitochondria-associated ferroptosis mediated by PKCα/NOX4 signaling, probably via VDR activation. VitD, alone or in combination with existing analgesics, presents an innovative therapeutic avenue for neuropathic pain.


Subject(s)
Cholecalciferol , Ferroptosis , Mitochondria , Neuralgia , Signal Transduction , Animals , Male , Rats , Cholecalciferol/pharmacology , Ferroptosis/drug effects , Ferroptosis/physiology , Hyperalgesia/drug therapy , Hyperalgesia/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , NADPH Oxidase 4/metabolism , NADPH Oxidase 4/antagonists & inhibitors , Neuralgia/drug therapy , Neuralgia/metabolism , Protein Kinase C-alpha/metabolism , Protein Kinase C-alpha/antagonists & inhibitors , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiology , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology
5.
BMC Plant Biol ; 24(1): 870, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39289615

ABSTRACT

BACKGROUND: Secretory carrier membrane proteins (SCAMPs) form a family of integral membrane proteins and play a crucial role in mediating exocytosis in both animals and plants. While SCAMP genes have been studied in several plant species, their functions in cotton, particularly in response to abiotic stress, have not yet been reported. RESULTS: In this study, a total of 53 SCAMP genes were identified in G. arboreum, G. raimondii, G. hirsutum, and G. barbadense. These genes were classified into five groups based on a phylogenetic analysis with SCAMPs from Arabidopsis thaliana. The main factor driving the expansion of the SCAMP gene family in G. hirsutum is tandem and segmental duplication events. Using MEME, in addition to the conserved SCAMP domain, we identified 3-13 other domains in each GhSCAMP. The cis-element analysis suggested that GhSCAMPs were widely involved in cotton growth and development, and responses to abiotic stresses. RNA sequencing (RNA-Seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results showed that most GhSCAMPs were expressed highly in many tissues and had differential expression responses to drought, cold, and heat stresses. Knock-down of GhSCAMP2 and GhSCAMP4 by virus-induced gene silencing (VIGS) lead to a salt-sensitive phenotype and had a lower content of CAT, POD, and SOD. CONCLUSIONS: This study identified SCAMP genes in four cotton species, enhancing our understanding of the potential biological functions of SCAMPs. Additionally, we demonstrated that GhSCAMP2 and GhSCAMP4 positively regulate cotton tolerance to salt stress.


Subject(s)
Gossypium , Phylogeny , Plant Proteins , Salt Tolerance , Gossypium/genetics , Gossypium/physiology , Salt Tolerance/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Stress, Physiological/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Genome, Plant
6.
Food Funct ; 15(18): 9420-9433, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39189524

ABSTRACT

The primary cause of mortality in colorectal cancer (CRC) patients is tumor metastasis. The epithelial-mesenchymal transition (EMT) stands out as a crucial factor promoting the metastasis of CRC. Previous findings suggest a potential inhibitory effect of docosahexaenoic acid (DHA) on CRC metastasis, but the precise mechanism remains unknown, this study aims to explore this issue. We assessed metastasis and recurrence, all-cause mortality, and cancer-related mortality rates according to DHA intake in independent CRC cohorts (n = 367) by survival analysis. The ability of DHA to block CRC cell migration and invasion was tested using transwell and wound-healing assays. The regulation of EMT marker genes in CRC by DHA was detected by quantitative real-time PCR (qPCR) and immunoblotting, and the effect of DHA on the TGF-ß1/Smad signaling pathway was further investigated. These cellular findings were validated using a subcutaneous CRC mouse model. Survival analyses showed that lower DHA intake was associated with a higher risk of CRC metastasis and a poorer prognosis. In vitro experiments showed that DHA inhibits the TGF-ß1/Smad signaling pathway and regulates downstream transcription factors, thereby reversing the EMT and inhibiting invasion and migration. In the mouse model, dietary DHA supplementation effectively increased blood DHA concentrations and inhibited CRC metastasis. Our study demonstrated that DHA inhibits CRC invasion and metastasis by inhibiting the TGF-ß1/Smad signaling pathway. Increased intake of DHA among CRC patients may provide additional benefits to the prognosis of colorectal cancer.


Subject(s)
Cell Movement , Colorectal Neoplasms , Docosahexaenoic Acids , Epithelial-Mesenchymal Transition , Signal Transduction , Smad Proteins , Transforming Growth Factor beta1 , Docosahexaenoic Acids/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effects , Humans , Animals , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Signal Transduction/drug effects , Cell Movement/drug effects , Mice , Smad Proteins/metabolism , Smad Proteins/genetics , Male , Female , Cell Line, Tumor , Middle Aged , Mice, Nude , Mice, Inbred BALB C , Aged , Neoplasm Invasiveness
7.
Carcinogenesis ; 45(10): 745-758, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39162797

ABSTRACT

Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched paracarcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In the ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of the transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.


Subject(s)
Colorectal Neoplasms , Proto-Oncogene Protein c-ets-1 , Tumor Microenvironment , Tumor-Associated Macrophages , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/immunology , Animals , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-ets-1/genetics , Humans , Mice , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Mice, Knockout , Macrophages/metabolism , Macrophages/immunology , Disease Progression , Proto-Oncogene Mas , Male , Gene Expression Regulation, Neoplastic
8.
Eur Radiol ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122854

ABSTRACT

OBJECTIVE: To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). METHODS: This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. RESULTS: A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. CONCLUSION: Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. CLINICAL RELEVANCE STATEMENT: Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. KEY POINTS: The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.

9.
J Ethnopharmacol ; 334: 118529, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-38972528

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sinisan formula (SNSF), documented in the classic books Shanghan Lun, is known for its ability to regulate liver-qi and treat depression. However, its underlying mechanism, particularly its effects on dynamic real-time neuron activity and circuits remains to be fully elucidated. AIM OF THE STUDY: This study aimed to investigate the antidepressant effect of SNSF and its central nervous system mechanism on depression-like behaviors, focusing on the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) neural circuit in a stress-induced adolescent animal model. MATERIALS AND METHODS: SNSF comprised four herbs, the root of Bupleurum chinense DC., the root of Paeonia lactiflora Pall., the fruit of Citrus aurantium L., the rhizome of Glycyrrhiza uralensis Fisch., in equal propotions. The adolescent depression animal model was induced by maternal separation (MS) and chronic restraint stress (CRS). In-vivo multichannel physiological electrodes were implanted into the PFC on PND 28 and animals were recorded 5 times during PND 35-46. From PND 47, the behavioral tests were performed to evaluate the antidepressant efficacy of SNSF. Subsequently, brain tissue was collected for Western blot and immunofluorescence staining analysis. Retro virus was injected into the DRN to explore sources of projections received by serotonergic (5-HTergic) neurons. And the PFC-to-DRN circuit was activated or inhibited through chemogenetic techniques to investigate the effects of SNSF on depression-like behaviors. RESULTS: Administration of SNSF for 18 days effectively alleviated depression-like behaviors in MS&CRS adolescent mice. The PFC emerged as the primary glutamatergic projection source of the DRN5-HT neurons. Following SNSF administration for 13/15/18 days, there was an increase in the firing rate of excitatory neurons and excitatory/inhibitory (E/I) ratio in the PFC. MS&CRS stress let to a reduction in the density of 5-HT+ and CaMKII + neurons in the DRN, accompanied by an increase in the density of GAD + neurons in the DRN, while SNSF administration reversed the alterations. Chemogenetic activation of the PFC-to-DRN circuit rescued the depression-like behaviors induced by MS&CRS, whereas suppression of this circuit attenuated the antidepressant effect of SNSF. CONCLUSIONS: SNSF significantly mitigated depression-like behaviors in MS&CRS mice. SNSF exerts its antidepressant effects by increasing the E/I ratio in the PFC and enhancing glutamatergic projections from the PFC to the DRN.


Subject(s)
Antidepressive Agents , Depression , Dorsal Raphe Nucleus , Drugs, Chinese Herbal , Prefrontal Cortex , Animals , Dorsal Raphe Nucleus/drug effects , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Antidepressive Agents/pharmacology , Male , Depression/drug therapy , Mice , Drugs, Chinese Herbal/pharmacology , Disease Models, Animal , Stress, Psychological/drug therapy , Behavior, Animal/drug effects , Neural Pathways/drug effects , Maternal Deprivation
10.
J Med Case Rep ; 18(1): 315, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982482

ABSTRACT

BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.


Subject(s)
Adenine , Leukemia, Lymphocytic, Chronic, B-Cell , Piperidines , Thalidomide , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Aged , Male , Female , Middle Aged , Adenine/analogs & derivatives , Piperidines/therapeutic use , Thalidomide/therapeutic use , Thalidomide/analogs & derivatives , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/secondary , Central Nervous System Neoplasms/diagnostic imaging , Pyrazoles/therapeutic use , Methotrexate/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pyrimidines/therapeutic use
11.
Noise Health ; 26(121): 142-147, 2024.
Article in English | MEDLINE | ID: mdl-38904814

ABSTRACT

OBJECTIVE: To investigate the effect of incorporating noise-canceling headphones into the delivery process for natural childbirth puerperae. METHODS: We conducted a retrospective analysis of clinical data encompassing natural childbirth puerperae in the People's Hospital of Suzhou New District from January 2021 to February 2023. The implementation of routine noise reduction management was done from January 2021 to January 2022. During this interval, 69 natural childbirth puerperae were selected as subjects, with 7 excluded, resulting in 62 participants constituting the reference group. Subsequently, noise-canceling headphones were distributed to natural childbirth puerperae from February 2022 to February 2023. In this phase, 66 subjects were selected, and 6 were excluded, resulting in 60 participants forming the observation group. Following admission, both groups underwent corresponding nursing management. Emotional states, pain levels, and various indicators were systematically collected and meticulously compared. RESULTS: The observation group exhibited significantly lower Hamilton Anxiety Rating Scale scores than the reference group before delivery and during the first stage of labor (P < 0.05). The observation group demonstrated significantly lower visual analog scale scores and substance P, nitric oxide, and prostaglandin E2 levels than the reference group during the first stage of labor (P < 0.001). During the second stage of labor, the visual analog) scale scores were significantly lower in the observation group than in the reference group (P < 0.05). The durations of first and second labor stages were significantly shorter in the observation group than in the reference group (P < 0.05). No significant difference existed in Apgar scores between the two groups (P > 0.05). CONCLUSION: The utilization of noise-canceling headphones emerges as an effective intervention, alleviating anxiety, reducing pain during T1, and abbreviating total labor time in natural childbirth puerperae, suggesting its substantial clinical application value and potential as a beneficial addition to maternity care practices.


Subject(s)
Natural Childbirth , Noise , Humans , Female , Pregnancy , Retrospective Studies , Adult , Natural Childbirth/methods , Noise/adverse effects , Delivery, Obstetric/methods , Ear Protective Devices , Anxiety/prevention & control , Anxiety/etiology
12.
Ann Hematol ; 2024 May 18.
Article in English | MEDLINE | ID: mdl-38761184

ABSTRACT

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

13.
CNS Neurosci Ther ; 30(5): e14745, 2024 05.
Article in English | MEDLINE | ID: mdl-38715326

ABSTRACT

BACKGROUND: Neuropathic pain remains a formidable challenge for modern medicine. The first-line pharmacological therapies exhibit limited efficacy and unfavorable side effect profiles, highlighting an unmet need for effective therapeutic medications. The past decades have witnessed an explosion in efforts to translate epigenetic concepts into pain therapy and shed light on epigenetics as a promising avenue for pain research. Recently, the aberrant activity of histone deacetylase (HDAC) has emerged as a key mechanism contributing to the development and maintenance of neuropathic pain. AIMS: In this review, we highlight the distinctive role of specific HDAC subtypes in a cell-specific manner in pain nociception, and outline the recent experimental evidence supporting the therapeutic potential of HDACi in neuropathic pain. METHODS: We have summarized studies of HDAC in neuropathic pain in Pubmed. RESULTS: HDACs, widely distributed in the neuronal and non-neuronal cells of the dorsal root ganglion and spinal cord, regulate gene expression by deacetylation of histone or non-histone proteins and involving in increased neuronal excitability and neuroinflammation, thus promoting peripheral and central sensitization. Importantly, pharmacological manipulation of aberrant acetylation using HDAC-targeted inhibitors (HDACi) has shown promising pain-relieving properties in various preclinical models of neuropathic pain. Yet, many of which exhibit low-specificity that may induce off-target toxicities, underscoring the necessity for the development of isoform-selective HDACi in pain management. CONCLUSIONS: Abnormally elevated HDACs promote neuronal excitability and neuroinflammation by epigenetically modulating pivotal gene expression in neuronal and immune cells, contributing to peripheral and central sensitization in the progression of neuropathic pain, and HDACi showed significant efficacy and great potential for alleviating neuropathic pain.


Subject(s)
Epigenesis, Genetic , Histone Deacetylase Inhibitors , Histone Deacetylases , Neuralgia , Humans , Epigenesis, Genetic/drug effects , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism
14.
Brief Funct Genomics ; 23(5): 672-678, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-38669080

ABSTRACT

Schizosaccharomyces pombe is a commonly utilized model organism for studying various aspects of eukaryotic cell physiology. One reason for its widespread use as an experimental system is the ease of genetic manipulations, leveraging the natural homology-targeted repair mechanism to accurately modify the genome. We conducted a study to assess the feasibility and efficiency of directly introducing exogenous genes into the fission yeast S. pombe using Polymerase Chain Reaction (PCR) with short-homology flanking sequences. Specifically, we amplified the NatMX6 gene (which provides resistance to nourseothricin) using PCR with oligonucleotides that had short flanking regions of 20 bp, 40 bp, 60 bp and 80 bp to the target gene. By using this purified PCR product, we successfully introduced the NatMX6 gene at position 171 385 on chromosome III in S. pombe. We have made a simple modification to the transformation procedure, resulting in a significant increase in transformation efficiency by at least 5-fold. The success rate of gene integration at the target position varied between 20% and 50% depending on the length of the flanking regions. Additionally, we discovered that the addition of dimethyl sulfoxide and boiled carrier DNA increased the number of transformants by ~60- and 3-fold, respectively. Furthermore, we found that the removal of the pku70+ gene improved the transformation efficiency to ~5% and reduced the formation of small background colonies. Overall, our results demonstrate that with this modified method, even very short stretches of homologous regions (as short as 20 bp) can be used to effectively target genes at a high frequency in S. pombe. This finding greatly facilitates the introduction of exogenous genes in this organism.


Subject(s)
Polymerase Chain Reaction , Schizosaccharomyces , Schizosaccharomyces/genetics , Polymerase Chain Reaction/methods , Transformation, Genetic
15.
PeerJ ; 12: e17203, 2024.
Article in English | MEDLINE | ID: mdl-38618570

ABSTRACT

Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.


Subject(s)
Antihypertensive Agents , Hypertension , Adult , Humans , Antihypertensive Agents/therapeutic use , Cross-Sectional Studies , Hypertension/drug therapy , Blood Pressure , Healthy Lifestyle
16.
Front Endocrinol (Lausanne) ; 15: 1302296, 2024.
Article in English | MEDLINE | ID: mdl-38577567

ABSTRACT

Background: Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. Methods: In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. Results: After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. Conclusion: This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.


Subject(s)
Adiposity , Hypertension , Humans , Cross-Sectional Studies , Multimorbidity , Body Mass Index , Obesity , Hypertension/epidemiology , Obesity, Abdominal
17.
Int J Mol Sci ; 25(6)2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38542145

ABSTRACT

Setaria italica is an important crop in China that plays a vital role in the Chinese dietary structure. In the last several decades, high temperature has become the most severe climate issue in the world, which causes great harm to the yield and quality formation of millet. In this study, two main cultivated varieties (ZG2 and AI88) were used to explore the photosynthesis and yield index of the whole plant under heat stress. Results implied that photosynthesis was not inhibited during the heat stress, and that the imbalance in sugar transport between different tissues may be the main factor that affects yield formation. In addition, the expression levels of seven SiSUT and twenty-four SiSWEET members were explored. Sugar transporters were heavily affected during the heat stress. The expression of SiSWEET13a was inhibited by heat stress in the stems, which may play a vital role in sugar transport between different tissues. These results provide new insights into the yield formation of crops under heat stress, which will provide guidance to crop breeding and cultivation.


Subject(s)
Setaria Plant , Setaria Plant/genetics , Setaria Plant/metabolism , Plant Breeding , Gene Expression Profiling , Heat-Shock Response/genetics , Sugars/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, Plant
18.
Front Public Health ; 12: 1345899, 2024.
Article in English | MEDLINE | ID: mdl-38476488

ABSTRACT

This systematic review was carried out to describe QoL and resilience in infertile patients, as well as the relationship between them, and to give a theoretical foundation for clinical practice. The databases of CNKI, Wanfang data, VIP database, PubMed, Web of Science, and Embase were searched without a time limit. A narrative synthesis of relevant articles was undertaken. This systematic review was registered on PROSPERO in advance. Of 21 studies eligible for inclusion in this review, 13 focused on the relationship between QoL and resilience, 5 on QoL influencing factors (resilience included), and 3 on mediation effect analysis on mental health (resilience as a mediator). Resilience can significantly predict the QoL of infertile patients. It seems plausible that more resilient couples will be less vulnerable to the stress of infertility. A global consortium of infertile population research could make cross-cultural comparisons of QoL and resilience possible. Future research should focus on resilience therapies. Systematic review registration: This systematic review was registered on PROSPERO in advance (CRD42023414706).


Subject(s)
Infertility , Quality of Life , Resilience, Psychological , Humans , Quality of Life/psychology , Infertility/psychology , Female , Male
19.
Plant Physiol Biochem ; 208: 108462, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38484683

ABSTRACT

NAC transcription factors regulate plant growth, development, and stress responses. However, the number, types, and biological functions of Limonium bicolor LbNAC genes have remained elusive. L. bicolor secretes excessive salt ions through salt glands on its stems and leaves to reduce salt-induced damage. Here, we identified 63 NAC members (LbNAC1-63) in L. bicolor, which were unevenly distributed across eight chromosomes. Cis-elements in the LbNAC promoters were related to growth and development, stress responses, and phytohormone responses. We observed strong colinearity between LbNACs and GmNACs from soybean (Glycine max). Thus, LbNAC genes may share similar functions with GmNAC genes. Expression analysis indicated that 16 LbNAC genes are highly expressed in roots, stems, leaves, and flowers, whereas 17 LbNAC genes were highly expressed throughout salt gland development, suggesting that they may regulate this developmental stage. Silencing LbNAC54 in L. bicolor decreased salt gland density, salt secretion from leaves, and overall salt tolerance. In agreement, genes related to salt gland development were significantly downregulated in LbNAC54-silenced lines. Our findings shed light on LbNAC genes and help elucidate salt gland development and salt secretion in L. bicolor. Our data also provide insight into NAC functions in halophytes.


Subject(s)
Plumbaginaceae , Salt-Tolerant Plants , Salt-Tolerant Plants/genetics , Salt-Tolerant Plants/metabolism , Plumbaginaceae/genetics , Plumbaginaceae/metabolism , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Leaves/metabolism , Glycine max , Gene Expression Regulation, Plant , Phylogeny
20.
Environ Sci Pollut Res Int ; 31(19): 27679-27688, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38517630

ABSTRACT

To evaluate the potential ecotoxicity of ethiprole and early warning to earthworms (Eisenia fetida), different concentrations (0 mg·kg-1, 416 mg·kg-1, 625 mg·kg-1, and 1000 mg·kg-1) of ethiprole were added to artificial soil. The key bioindicators were measured and screened at 3 days, 7 days, 14 days, 21 days, and 28 days. The results show that the activity of catalase (CAT) was inhibited for all treatments during the whole exposure period. Besides, the olive tail moment (OTM) value increased gradually as the concentration got higher, which exhibited a dose-time-dependent relationship. Superoxide dismutase (SOD) gene reached the maximum on the 7th day. Mitochondrial large ribosomal RNA (l-rRNA) subunit gene was always in a downregulated state as the concentration increased. Our results show that different concentrations of ethiprole induced certain oxidative stress, DNA damage, and genotoxicity in earthworms. The CAT activity, OTM, and SOD gene could be the most sensitive biomarkers to monitor the toxicity of ethiprole in the soil.


Subject(s)
DNA Damage , Oligochaeta , Oxidative Stress , Animals , Oligochaeta/drug effects , Oligochaeta/genetics , Oxidative Stress/drug effects , Gene Expression/drug effects , Soil Pollutants/toxicity , Superoxide Dismutase/metabolism , Catalase/metabolism
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