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1.
Neural Regen Res ; 20(2): 402-415, 2025 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819044

RESUMO

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38956905

RESUMO

BACKGROUND: Spindle cell carcinoma (SCC) of the breast is a rare type of metaplastic carcinoma with poor prognosis, high recurrence, and distant metastasis. Mammectomy, chemotherapy, radiotherapy, and endocrine therapy are the preferred choices of treatments. Tumor-infiltrating lymphocyte (TIL) therapy, which utilizes the patient's immune cells from the solid tumor micro-environment to eradicate cancer cells, has shown promising results in treating advanced solid tumors. However, its use for SCC of the breast has not been reported. CASE PRESENTATION: Here, we present a case of combining TIL therapy with personalized chemotherapy and endocrine therapy for the treatment of SCC of the breast. A 36-year-old Chinese woman presented with a palpable nodule (32 mm) on her left breast. Based on histological and immunohistochemical analysis of breast biopsy and surgical specimens, she was diagnosed with SCC of the breast (stage IIA). The patient received concurrent personalized chemotherapy, TIL therapy, and endocrine therapy following mammectomy. She showed no severe side effects during therapy, and did not present local recurrence or distant metastasis after follow-up for at least 14 months. CONCLUSION: To our knowledge, this is the first case report, which demonstrated that TIL therapy combined with chemotherapy/endocrine therapy after mastectomy is safe and effective for SCC of the breast.

3.
Stem Cell Res ; 79: 103486, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38968760

RESUMO

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

4.
Insect Mol Biol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961541

RESUMO

Animal silk is economically important, while silk secretion is a complex and subtle mechanism regulated by many genes. We identified the poly (ADP-ribose) polymerase (PARP1) gene of the silkworm and successfully cloned its coding sequence (CDS) sequence. Using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9) technology, we screened single guide RNA (sgRNA) with high knockout efficiency by cellular experiments and obtained PARP1 mutants by knocking out the PARP1 gene of the silkworm at the individual level. We found that the mutants mainly exhibited phenotypes such as smaller cocoon size and reduced cocoon shell rate than the wild type. We also detected the expression of silk protein genes in the mutant by quantitative real-time PCR (qPCR) and found that the expression of some silk protein genes was slightly down-regulated. Meanwhile, together with the results of transcriptomic analysis, we hypothesized that PARP1 may affect the synthesis of silk proteins, resulting in their failure to function properly. Our study may provide an important reference for future in-depth refinement of the molecular mechanism of silk protein expression in silk-producing animals, as well as a potential idea for future development of molecular breeding lines of silkworms to improve silk production.

5.
Food Chem ; 459: 140370, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38986208

RESUMO

Due to the excellent health benefits of rhamnogalacturonan I (RG-I)-enriched pectin, there has been increasing research interest in its gelling properties. To elucidate its structure-gelation relationship, chemical modifications were used to obtain RG-I-enriched pectin (P11). Then, enzymatic modification was performed to obtain debranched pectins GP11 and AP11, respectively. The effects of RG-I side chains on structural characteristics (especially spatial conformation) and gelling properties were investigated. Among the low-methoxylated pectins (LMPs), AP11, with a loose conformation (Dmax 52 nm) showed the poorest gelling, followed by GP11. In addition to primary structure, spatial conformation (Dmax and Rg) also showed strong correlations (r2 > 0.8) with gelation. We speculate that compact conformation may shorten distance between pectin chains and reduces steric hindrance, contributing to formation of strong gel network. This is particularly important in LMPs with abundant side chains. The results provide novel insights into relationship between spatial conformation and gelling properties of RG-I-enriched pectin.

6.
Heliyon ; 10(12): e32971, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38994055

RESUMO

In recent years, despite the fact that the Chinese government is closely monitoring food safety, the perception of food production enterprises is not obvious. The reason is that information asymmetry hinders the effective transmission of regulatory information to food production enterprises. In the present research, a choice test is conducted to explore the preference of decision-makers for the information on government regulations in 224 food production enterprises with violations. It is found out that the decision-makers of food production enterprises have a strong preference for the regulatory information released by local governments. With a preference for reference information, compared to those who violate the law just once, decision-makers in food production companies that have several infractions exhibit a high "reference dependence" mentality. Also, the preference of different decision-maker characteristics shows an evident heterogeneity, as does the preference of various enterprises for the regulatory information about food safety. It is recommended that the government should improve the mechanism of disclosing the information about food safety, and focus on tailoring the information to different types of enterprises.

7.
J Perianesth Nurs ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39001741

RESUMO

PURPOSE: This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DESIGN: Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. METHODS: A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FINDINGS: The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. CONCLUSIONS: The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

8.
Cell ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971151

RESUMO

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

9.
Theor Appl Genet ; 137(8): 179, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980436

RESUMO

Rust diseases, including leaf rust, stripe/yellow rust, and stem rust, significantly impact wheat (Triticum aestivum L.) yields, causing substantial economic losses every year. Breeding and deployment of cultivars with genetic resistance is the most effective and sustainable approach to control these diseases. The genetic toolkit for wheat breeders to select for rust resistance has rapidly expanded with a multitude of genetic loci identified using the latest advances in genomics, mapping and cloning strategies. The goal of this review was to establish a wheat genome atlas that provides a comprehensive summary of reported loci associated with rust resistance. Our atlas provides a summary of mapped quantitative trait loci (QTL) and characterised genes for the three rusts from 170 publications over the past two decades. A total of 920 QTL or resistance genes were positioned across the 21 chromosomes of wheat based on the latest wheat reference genome (IWGSC RefSeq v2.1). Interestingly, 26 genomic regions contained multiple rust loci suggesting they could have pleiotropic effects on two or more rust diseases. We discuss a range of strategies to exploit this wealth of genetic information to efficiently utilise sources of resistance, including genomic information to stack desirable and multiple QTL to develop wheat cultivars with enhanced resistance to rust disease.


Assuntos
Basidiomycota , Mapeamento Cromossômico , Resistência à Doença , Doenças das Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Resistência à Doença/genética , Basidiomycota/patogenicidade , Melhoramento Vegetal , Genoma de Planta , Genes de Plantas , Cromossomos de Plantas/genética
10.
Front Neurosci ; 18: 1388213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39010942

RESUMO

Objective: Acute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients. Methods: Data of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson's partial correlation. Results: Compared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = -0.434). Conclusion: Our results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

11.
Redox Biol ; 75: 103267, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39025016

RESUMO

Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.

12.
J Cardiothorac Surg ; 19(1): 453, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014449

RESUMO

BACKGROUND: With a considerable variety of cancer subtypes, Non-small cell lung cancer (NSCLC) poses a substantial threat to public health, affecting a large number of individuals and resulting in a high mortality rate. Circular RNA (circRNA) has been applied in various diseases, including cancers. This study aims to investigate the clinial significance and functional role of circPTP4A2 in NSCLC. METHODS: The serum and tissue samples were collected for detecting circPTP4A2 expression in NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Actinomycin D was used to treat NSCLC cells to detect circPTP4A2 stability. The CCK-8 and Transwell assays were utilized to assess the effects of circPTP4A2 in NSCLC cells. The ELISA assay and cytotoxicity analysis were used to detect the roles of circPTP4A2 in immune escape. RESULTS: The serum and tissue circPTP4A2 expression was upregulated in NSCLC. The high circPTP4A2 had a relatively high value in differentiating NSCLC patients from healthy individuals. The proliferation, invasion, and immune escape were repressed by circPTP4A2 knockdown. CONCLUSIONS: High circPTP4A2 has the potential to be a diagnostic biomarker in NSCLC. Silencing of circPTP4A2 receded the progression of NSCLC and enhanced antitumor immunity, which might provide potential targets and new ideas for improving the diagnosis and effect of immunotherapy in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Neoplasias Pulmonares , RNA Circular , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , RNA Circular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Técnicas de Silenciamento de Genes
13.
Am J Obstet Gynecol MFM ; : 101433, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019211

RESUMO

BACKGROUND: Improved pain control after caesarean section remains a challenging objective. Although both the lateral quadratus lumborum block and acupuncture have been reported to provide superior postoperative analgesia after caesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of lateral quadratus lumborum block and acupuncture following elective caesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton term pregnancies scheduled for caesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or lateral quadratus lumborum block group. Lateral quadratus lumborum block group received bilateral lateral quadratus lumborum block with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy and sham lateral quadratus lumborum block. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 h. Secondary endpoints included pain scores in the first 48 h postoperatively, patient-controlled intravenous analgesia demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (IQR [range]) pain scores at 24 h on movement was similar in patients receiving acupuncture or lateral quadratus lumborum block (3 (2-4) vs. 3 (2-4), respectively; P = 0.40). Patient-controlled intravenous analgesia consumption and pain scores within 48 h postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 h postoperatively (P<0.001), as well as shortened the time to first flatus (P=0.03) and first drinking (P<0.001) compared to lateral quadratus lumborum block. In addition, the median time to mobilization in the lateral quadratus lumborum block group was markedly prolonged compare with acupuncture group (17.0 (15.0-19.0) h vs. 15.3 (13.3-17.0) h, estimated median difference, 1.5; 95%CI, 1-2; P<0.001;). CONCLUSIONS: As a component of multimodal analgesia regimen after caesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to lateral quadratus lumborum block.

14.
World Neurosurg ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033809

RESUMO

OBJECTIVE: To compare the safety, clinical outcomes and radiological results of anterior cervical discectomy and fusion (ACDF) with zero-profile anchored spacer (ZPAS) versus plate and cage (PC) for three-level contiguous cervical degenerative disease (CDD). METHODS: The study was registered at PROSPERO (CRD42024512706). The Web of Science core collection, PubMed and Embase were searched up to February 12, 2024. Review Manager 5.3 was used. The relative risk (RR) and 95% confidence interval (CI) was evaluated for dichotomous data. Continuous data were assessed using the mean difference (MD) and 95% CI. RESULTS: Nine studies comparing ACDF with ZPAS versus PC for three-level contiguous CDD were included. The intraoperative blood loss and operation time in ZPAS were significantly less than those in PC. The subsidence rate, loss of cervical alignment, fusion segmental height and intervertebral disc height were significantly greater in ZPAS than in PC. The cervical alignment and dysphagia rate within 6 months were significantly lower in ZPAS than in PC. The ASD of ZPAS was significantly lower than that of PC according to the sensitivity analysis when one study was excluded. No significant differences were identified in the other aspects. CONCLUSION: Both ACDF with ZPAS and PC were safe and effective procedures. PC was associated with increased surgical trauma. The ZPAS could better decrease the incidence of ASD and dysphagia. ZPAS was also accompanied by high subsidence rate and poor cervical alignment.

15.
Transl Psychiatry ; 14(1): 297, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030164

RESUMO

Methylmalonic acid (MMA), a biomarker of mitochondrial dysfunction, has been reported to be associated with depression in specific populations (i.e., older adults and postpartum women). Our study aimed to investigate to what extent MMA was associated with depressive symptoms and mortality in the general population, and assess whether depressive symptoms mediate the relationship between MMA and mortality. We analyzed cross-sectional data from 8343 participants from the US National Health and Nutrition Examination Survey. MMA was measured by liquid chromatography-tandem mass spectrometry, while depressive symptoms were measured by the Patient Health Questionnaire-9. Mortality data were obtained through linkage with National Death Index records. Linear regression models were performed to assess the association between MMA and depressive symptoms. The Cox proportional hazard regression model was utilized to assess the association of MMA and depressive symptoms with mortality. Mediation analysis was conducted within the counterfactual framework. In this general population, each SD (around 0.49 µmol/L) increase in MMA was associated with a 0.03 SD (approximately 0.15 score) increase in depressive symptoms (ß = 0.033, 95% CI: 0.010, 0.055, p = 0.005). Notably, this association was more pronounced in men and participants over 60 years old. Higher levels of MMA and having more depressive symptoms were associated with a higher risk of mortality. However, depressive symptoms do not mediate the relationship between MMA and mortality. Elevated MMA levels were associated with depressive symptoms and an increased risk of mortality. These findings suggest that mitochondrial dysfunction may contribute to the multifactorial etiology of depression.


Assuntos
Depressão , Ácido Metilmalônico , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Ácido Metilmalônico/sangue , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Idoso , Estados Unidos/epidemiologia , Modelos de Riscos Proporcionais , Biomarcadores/sangue , Mortalidade
16.
Gene ; 928: 148763, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002784

RESUMO

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

18.
Nat Commun ; 15(1): 6071, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025880

RESUMO

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.


Assuntos
Biomarcadores Tumorais , Ilhas de CpG , Metilação de DNA , Estudo de Associação Genômica Ampla , Neoplasias , Especificidade de Órgãos , Humanos , Ilhas de CpG/genética , Neoplasias/genética , Masculino , Feminino , Biomarcadores Tumorais/genética , Especificidade de Órgãos/genética , Predisposição Genética para Doença , Regulação Neoplásica da Expressão Gênica , Epigênese Genética , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares
19.
Int J Neurosci ; : 1-10, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38963402

RESUMO

PURPOSE: To evaluate cardiorespiratory fitness in patients with early to mid-stage Parkinson's disease by cardiopulmonary exercise test (CPET) on a stationary cycle ergometer. METHODS: To compare the differences in each index of the cardiopulmonary exercise test between the two groups of subjects; general data such as disease duration, medication use and exercise habits were also collected. RESULTS: (1) Finally, 36 Parkinson's disease patients and 12 healthy controls successfully completed the cardiopulmonary exercise test without any adverse events. (2) The V'O2peak, Metspeak, RERpeak, MVVpeak, Wpeak, HRpeak, HRpeak/pre, percentage of HRR-1 min decay > 12 bpm, SBPpeak in the Parkinson's disease group were lower than those in the control group (p < .05, each). Detailed data: V'O2peak (15.7 ± 4.5vs21.5 ± 3.6 ml/kg/min, p < .01), Metspeak (4.5 ± 1.3 vs 6.1 ± 1.0, p < .01), RERpeak (1.04 ± 0.10 vs 1.15 ± 0.10, p = .001), MVVpeak (37.22 ± 11.58 vs 53.00 ± 16.85L/min, p = .009), Wpeak (49.17 ± 29.72 vs 49.17 ± 29.72W, p < .01), HRpeak (111.08 ± 16.67 vs 111.08 ± 16.67bpm, p < .01), HRpeak/pre (71.19 ± 10.06 vs 96.00 ± 21.13, p = .002), percentage of HRR-1min decay > 12bpm (33.3% vs 100%, p < .01), systolic blood pressure (155.81 ± 31.83 vs 175.83 ± 17.84 mmHg, p = .01). (3) Divided Parkinson's disease patients into high V'O2peak group (V'O2peak ≥ 15 mL/kg/min) and low V'O2peak group (V'O2peak < 15 mL/kg/min). The age of patients, Hoehn-Yahr grade and incidence of symptom fluctuation in high V'O2peak group were lower (p < .05, respectively), percentage of males and percentage of HRR-1 min decay > 12 bpm were higher (p < .05, respectively); p < .05 is considered a statistically significant difference. Detailed data: age of patients(61.05 ± 6.93 vs 68.57 ± 7.99 years, p = .005), Hoehn-Yahr grade(1.75 ± 0.48 vs 2.18 ± 0.64, p = .028), incidence of symptom fluctuation (59.1 vs 92.9%, p = .03), percentage of males (77.7 vs 42.9%, p = .041), percentage of HRR-1 min decay > 12 bpm (50 vs 7.1%, p = .008). CONCLUSIONS: Cardiopulmonary exercise test was safe to perform and the cardiorespiratory fitness is significantly reduced in patients with early and middle stage Parkinson's disease. Patients with Parkinson's disease presented blunted heart rate and systolic blood pressure responses to exercise test. Females, older age, fluctuating symptoms, high H-Y staging and higher activities of daily living may be associated with lower oxygen uptake.

20.
Molecules ; 29(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998960

RESUMO

The United Nations proposed the Sustainable Development Goals with the aim to make human settlements in cities resilient and sustainable. The excessive discharge of urban waste including sludge and garden waste can pollute groundwater and lead to the emission of greenhouse gases (e.g., CH4). The proper recycling of urban waste is essential for responsible consumption and production, reducing environmental pollution and addressing climate change issues. This study aimed to prepare biochar with high adsorption amounts of iodine using urban sludge and peach wood from garden waste. The study was conducted to examine the variations in the mass ratio between urban sludge and peach wood (2/1, 1/1, and 1/2) as well as pyrolysis temperatures (300 °C, 500 °C, and 700 °C) on the carbon yield and adsorption capacities of biochar. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectrometry, powder X-ray diffraction, and elemental analysis were used to characterize the biochar produced at different pyrolysis temperatures and mass ratios. The results indicate that the carbon yield of biochar was found to be the highest (>60%) at a pyrolysis temperature of 300 °C across different pyrolysis temperatures. The absorbed amounts of iodine in the aqueous solution ranged from 86 to 223 mg g-1 at a mass ratio of 1:1 between urban sludge and peach wood, which were comparably higher than those observed in other mass ratios. This study advances water treatment by offering a cost-effective method by using biochar derived from the processing of urban sludge and garden waste.


Assuntos
Carvão Vegetal , Iodo , Pirólise , Esgotos , Carvão Vegetal/química , Iodo/química , Esgotos/química , Adsorção , Temperatura , Jardins , Espectroscopia de Infravermelho com Transformada de Fourier , Cidades
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