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1.
Lancet Rheumatol ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39089297

ABSTRACT

Common to all inflammatory arthritides, namely rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis, is a potential for reduced mobility that manifests through joint pain, swelling, stiffness, and ultimately joint damage. Across these conditions, consensus has been reached on the need to capture outcomes related to mobility, such as functional capacity and physical activity, as core domains in randomised controlled trials. Existing endpoints within these core domains rely wholly on self-reported questionnaires that capture patients' perceptions of their symptoms and activities. These questionnaires are subjective, inherently vulnerable to recall bias, and do not capture the granularity of fluctuations over time. Several early adopters have integrated sensor-based digital health technology (DHT)-derived endpoints to measure physical function and activity in randomised controlled trials for conditions including Parkinson's disease, Duchenne's muscular dystrophy, chronic obstructive pulmonary disease, and heart failure. Despite these applications, there have been no sensor-based DHT-derived endpoints in clinical trials recruiting patients with inflammatory arthritis. Borrowing from case studies across medicine, we outline the opportunities and challenges in developing novel sensor-based DHT-derived endpoints that capture the symptoms and disease manifestations most relevant to patients with inflammatory arthritis.

3.
J Virol ; : e0063524, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39158346

ABSTRACT

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.

4.
MedComm (2020) ; 5(9): e661, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39156767

ABSTRACT

In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S-catalyzing enzymes, such as cystathionine-ß-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

5.
Nanomaterials (Basel) ; 14(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39120341

ABSTRACT

We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 ↔ Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.

6.
Biomark Med ; : 1-9, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136444

ABSTRACT

Aim: To investigate the association between plasma AAT level and glaucoma. Methods: 163 glaucoma patients and 111 healthy controls were recruited. The plasma AAT levels were measured by ELISA. Results: Plasma AAT level was significantly higher in glaucoma patients than those in healthy controls (p < 0.001). Patients with higher plasma AAT level exhibited severer disease stage (early vs. severe: p < 0.05; H-P-A; early vs. severe: p < 0.05; early vs. end-stage: p < 0.01; AGIS). ROC curves yielded that AAT can distinguish patients with early glaucoma from those with advanced glaucoma (early vs. severe: AUC: 0.616; H-P-A; early vs. severe: AUC: 0.763; early vs. end-stage: AUC: 0.660; AGIS). Conclusion: Plasma AAT is a useful biomarker for the identification of glaucoma severity.


[Box: see text].

7.
Nat Commun ; 15(1): 6986, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143044

ABSTRACT

In the pursuit of scalable and energy-efficient neuromorphic devices, recent research has unveiled a novel category of spiking oscillators, termed "thermal neuristors." These devices function via thermal interactions among neighboring vanadium dioxide resistive memories, emulating biological neuronal behavior. Here, we show that the collective dynamical behavior of networks of these neurons showcases a rich phase structure, tunable by adjusting the thermal coupling and input voltage. Notably, we identify phases exhibiting long-range order that, however, does not arise from criticality, but rather from the time non-local response of the system. In addition, we show that these thermal neuristor arrays achieve high accuracy in image recognition and time series prediction through reservoir computing, without leveraging long-range order. Our findings highlight a crucial aspect of neuromorphic computing with possible implications on the functioning of the brain: criticality may not be necessary for the efficient performance of neuromorphic systems in certain computational tasks.

8.
Plants (Basel) ; 13(15)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39124279

ABSTRACT

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a crop of significant interest due to its nutritional value and resilience to drought conditions. However, drought, particularly following flowering, is a major factor contributing to yield reduction. This research employed two distinct Tartary buckwheat genotypes to investigate the effects of post-anthesis drought on growth and physicochemical characteristics. The study aimed to elucidate the response of Tartary buckwheat to drought stress. The findings indicated that post-anthesis drought adversely impacted the growth, morphology, and biomass accumulation of Tartary buckwheat. Drought stress enhanced the maximum photosynthetic capacity (Fv/Fm) and light protection ability (NPQ) of the 'Xiqiao-2' genotype. In response to drought stress, 'Dingku-1' and 'Xiqiao-2' maintained osmotic balance by accumulating soluble sugars and proline, respectively. Notably, 'Xiqiao-2' exhibited elevated levels of flavonoids and polyphenols in its leaves, which helped mitigate oxidative damage caused by drought. Furthermore, rewatering after a brief drought period significantly improved plant height, stem diameter, and biomass accumulation in 'Dingku-1'. Overall, 'Xiqiao-2' demonstrated greater long-term tolerance to post-anthesis drought, while 'Dingku-1' was less adversely affected by short-term post-anthesis drought.

9.
BMC Genomics ; 25(1): 797, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179980

ABSTRACT

BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.


Subject(s)
Gene Expression Regulation, Plant , Oryza , Phylogeny , Plant Proteins , Salt Stress , Transcription Factors , Oryza/genetics , Oryza/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Salt Stress/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Multigene Family , Gene Expression Profiling , Chromosomes, Plant/genetics
10.
Huan Jing Ke Xue ; 45(8): 4589-4599, 2024 Aug 08.
Article in Chinese | MEDLINE | ID: mdl-39168678

ABSTRACT

Dissolved carbon in groundwater plays an important role in carbon cycling and ecological function maintenance, and its concentration level affects the migration and transformation of pollutants in groundwater. To understand the spatiotemporal variation characteristics of dissolved carbon and its driving factors in shallow groundwater around plateau lakes, variations in the concentrations of dissolved organic carbon (DOC), inorganic carbon (DIC), and total carbon (DTC) and their driving factors in shallow groundwater (n = 404) around eight plateau lakes were analyzed. The results indicated that the average values of ρ(DOC), ρ(DIC), and ρ(DTC) in shallow groundwater around plateau lakes were 8.23, 49.01, and 57.84 mg·L-1, respectively, with the ρ(DOC) in 79.0% of shallow groundwater samples exceeding 5 mg·L-1. There were no significant differences in the DOC, DIC, and DTC concentrations between rainy and dry seasons, whereas the change in dissolved carbon concentrations in shallow groundwater were strongly affected by the intensity of agricultural intensification and the depth of groundwater table; the DOC, DIC, and DTC concentrations in shallow groundwater from facility agricultural regions (SFAR), cropland fallow agricultural regions (CFAR), and intensive agricultural regions with deeper groundwater tables (DIAR) were significantly reduced by 25.8% - 56.6%, 14.0% - 32.9%, and 16.6% - 36.7%, respectively, compared with those in intensive agricultural regions with shallower groundwater tables (SIAR). Additionally, the dissolved carbon concentrations in shallow groundwater from DIAR were significantly lower than those of SFAR and CFAR. RDA revealed that physicochemical factors in water and soil significantly explained the changes in the dissolved carbon concentrations. Moreover, the dissolved carbon concentrations in shallow groundwater around Yilong Lake were significantly higher than those of other lakes, whereas that of Chenghai Lake was significantly lower than that of other lakes. Our study highlights that agricultural intensification intensity and groundwater table depth jointly drove the variations in dissolved carbon concentrations in shallow groundwater around plateau lakes. The study results are expected to provide a scientific basis for understanding the carbon cycle in plateau lake areas with underground runoff flowing into lakes and evaluating the attenuation of pollutants by dissolved carbon in shallow groundwater.

11.
Food Chem ; 461: 140907, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39173266

ABSTRACT

Tartary buckwheat sprouts are highly valued by consumers for their superior nutritional content. Ionic titanium (Ti) has been shown to enhance crop growth and improve nutritional quality. However, there is limited research on the impact of ionic Ti on the nutritional quality of Tartary buckwheat sprouts. This study cultivated Tartary buckwheat sprouts with ionic Ti and found that the high concentration of ionic Ti significantly increased the contents of chlorophyll a, chlorophyll b, and carotenoids (increased by 25.5%, 27.57%, and 15.11%, respectively). The lower concentration of ionic Ti has a higher accumulation of total flavonoids and total polyphenols. Metabolomics analysis by LC-MS revealed 589 differentially expressed metabolites and 54 significantly different metabolites, enriching 82 metabolic pathways, especially including amino acid biosynthesis and flavonoid biosynthesis. This study shows that ionic Ti can promote the growth of Tartary buckwheat sprouts, improve nutritional quality, and have huge development potential in food production.

12.
BMC Pulm Med ; 24(1): 329, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982416

ABSTRACT

BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.


Subject(s)
Embolization, Therapeutic , Image-Guided Biopsy , Lung , Pneumothorax , Pulmonary Emphysema , Tomography, X-Ray Computed , Humans , Pneumothorax/etiology , Pneumothorax/prevention & control , Pneumothorax/epidemiology , Female , Male , Retrospective Studies , Aged , Middle Aged , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/methods , Embolization, Therapeutic/methods , Lung/pathology , Lung/diagnostic imaging , Risk Factors , Logistic Models , Chest Tubes , Gelatin Sponge, Absorbable/administration & dosage , Incidence , Multivariate Analysis , Aged, 80 and over , Radiography, Interventional/methods
13.
World J Gastrointest Surg ; 16(6): 1527-1536, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983348

ABSTRACT

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has emerged as a promising alternative compared to conventional laparoscopic-assisted total gastrectomy (LATG) for treating gastric cancer (GC). However, evidence regarding the efficacy and safety of NOSES for GC surgery is limited. This study aimed to compare the safety and feasibility, in addition to postoperative complications of NOSES and LATG. AIM: To discuss the postoperative effects of two different surgical methods in patients with GC. METHODS: Dual circular staplers were used in Roux-en-Y digestive tract reconstruction for transvaginal specimen extraction LATG, and its outcomes were compared with LATG in a cohort of 51 GC patients with tumor size ≤ 5 cm. The study was conducted from May 2018 to September 2020, and patients were categorized into the NOSES group (n = 22) and LATG group (n = 29). Perioperative parameters were compared and analyzed, including patient and tumor characteristics, postoperative outcomes, and anastomosis-related complications, postoperative hospital stay, the length of abdominal incision, difference in tumor type, postoperative complications, and postoperative survival. RESULTS: Postoperative exhaust time, operation duration, mean postoperative hospital stay, length of abdominal incision, number of specific staplers used, and Brief Illness Perception Questionnaire score were significant in both groups (P < 0.01). In the NOSES group, the postoperative time to first flatus, mean postoperative hospital stay, and length of abdominal incision were significantly shorter than those in the LATG group. Patients in the NOSES group had faster postoperative recovery, and achieved abdominal minimally invasive incision that met aesthetic requirements. There were no significant differences in gender, age, tumor type, postoperative complications, and postoperative survival between the two groups. CONCLUSION: The application of dual circular staplers in Roux-en-Y digestive tract reconstruction combined with NOSES gastrectomy is safe and convenient. This approach offers better short-term outcomes compared to LATG, while long-term survival rates are comparable to those of conventional laparoscopic surgery.

14.
Pestic Biochem Physiol ; 203: 105996, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39084770

ABSTRACT

Thiacloprid, a neonicotinoid insecticide, has become one of the major control agents for the pine sawyer beetle, Monochamus alternatus Hope, however, the mechanism of detoxification is unknown. We demonstrate that glutathione S-transferases (GSTs) and nicotinic acetylcholine receptors (nAChRs) are involved in the rapid detoxification of thiacloprid in M. alternatus larvae. The activity of detoxification enzyme GSTs was significantly higher, while the activity of acetylcholinesterase (AChE) was inhibited under thiacloprid exposure. The inhibition of AChE activity led to lethal over-stimulation of the cholinergic synapse, which was then released by the rapid downregulation of nAChRs. Meanwhile, GSTs were overexpressed to detoxify thiacloprid accordingly. A total of 3 nAChR and 12 GST genes were identified from M. alternatus, among which ManAChRα2 and MaGSTs1 were predicted to confer thiacloprid tolerance. RNA interference (RNAi) was subsequently conducted to confirm the function of ManAChRα2 and MaGSTs1 genes in thiacloprid detoxification. The successful knock-down of the ManAChRα2 gene led to lower mortality of M. alternatus under LC30 thiacloprid treatment, and the suppression of the MaGSTs1 gene increased the mortality rate of M. alternatus. However, the mortality rate has no significant difference with controls when thiacloprid was fed together with both dsMaGSTs1 and dsManAChRα2. Molecular docking modeled the molecular basis for interaction between MaGSTs1/ManAChR and thiacloprid. This study highlights the important roles that ManAChRα2 and MaGSTs1 genes play in thiacloprid detoxification through transcriptional regulation and enzymatic metabolization, and proposes a new avenue for integrated pest management that combines pesticides and RNAi technology as an efficient strategy for M. alternatus control.


Subject(s)
Coleoptera , Glutathione Transferase , Insecticides , Neonicotinoids , Receptors, Nicotinic , Thiazines , Animals , Neonicotinoids/pharmacology , Receptors, Nicotinic/metabolism , Receptors, Nicotinic/genetics , Coleoptera/drug effects , Coleoptera/genetics , Coleoptera/metabolism , Thiazines/pharmacology , Thiazines/metabolism , Thiazines/toxicity , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Insecticides/toxicity , Insecticides/pharmacology , Insecticides/metabolism , Larva/drug effects , Larva/metabolism , Insect Proteins/metabolism , Insect Proteins/genetics , Inactivation, Metabolic , Acetylcholinesterase/metabolism , Acetylcholinesterase/genetics , Pyridines/pharmacology
16.
J Dent Sci ; 19(3): 1801-1810, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39035263

ABSTRACT

Background/purpose: Periodontal breakdown in periodontitis is exacerbated by pro-inflammatory responses of periodontal stromal cells such as periodontal ligament fibroblasts (PDLFs). Procyanidin B2 (PB2) is a ligand of the peroxisome proliferator-activated receptor (PPARγ). Herein, we investigated the expression of PPARγ isoforms in PDLFs and periodontal tissue, and examined the effects of PB2 on PPARγ isoform-dependent antiinflammatory responses. Materials and methods: PPARγ isoforms were examined by PCR. PPARγ isoform-dependent inflammatory functions and anti-inflammatory effects of PB2 in PDLFs were evaluated based on IL-6 expression. Co-immunoprecipitation analysis of fixed chromatin-tethered protein (CoIPfctp) was conducted to investigate the association of each PPARγ isoform with the NF-κB-transcriptional complex. The effects of PB2 on periodontitis progression were evaluated using a ligature-induced murine periodontitis model. Results: Three isoforms of PPARγ were expressed in PDLFs and periodontal tissues, consisting of the main full-length isoform (PPARγ) and two dominant negative isoforms that lack the ligand binding domain, namely the ubiquitously-expressed isoform (PPARγ-UBI) and unknown isoform (PPARγ-PDL). PPARγ and PPARγ-UBI were predominantly expressed. CoIP-fctp revealed that PPARγ-UBI was selectively associated with NF-κB p65, a key transcriptional factor of IL-6 expression. PB2 suppressed LPS-induced-IL-6 expression exacerbated by the over-expression of PPARγ-UBI. In the murine periodontitis model, topical application of PB2 significantly mitigated alveolar bone loss. Conclusion: These results suggest that the anti-inflammatory effects of PB2 in periodontal tissues/cells are distinct, and these effects arise from the inhibition of PPARγ-UBI; hence, the application of PB2 and modification of the splicing event in three PPARγ isoforms have therapeutic potential for preventing periodontitis.

17.
Article in English | MEDLINE | ID: mdl-39041626

ABSTRACT

Significance: Ferroptosis, a form of regulated cell death characterized by a large amount of lipid peroxidation-mediated membrane damage, joins the evolution of multisystem diseases, for instance, neurodegenerative diseases, chronic obstructive pulmonary disease, acute respiratory distress syndrome, osteoporosis, osteoarthritis, and so forth. Since being identified as the third gasotransmitter in living organisms, the intricate role of hydrogen sulfide (H2S) in ferroptosis has emerged at the forefront of research. Recent Advances: Novel targets in the relevant metabolic pathways have been found, including transferrin receptor 1, cystine/glutamate antiporter, and others, coupled with the exploration of new signaling pathways, particularly the p53 signaling pathway, the nitric oxide/nuclear factor erythroid 2-related factor 2 signaling pathway, and so on. Many diseases such as emphysema and airway inflammation, myocardial diseases, endothelial dysfunction in aging arteries, and traumatic brain injury have recently been found to be alleviated directly by H2S inhibition of ferroptosis. Safe, effective, and tolerable novel H2S donors have been developed and have shown promising results in phase I clinical trials. Critical Issues: Complicated cross talk between the ferroptosis signaling pathway and oncogenic factors results in the risk of cancer when inhibiting ferroptosis. Notably, targeted delivery of H2S is still a challenging task. Future Directions: Discovering more reliable and stable novel H2S donors and achieving their targeted delivery will enable further clinical trials for diseases associated with ferroptosis inhibition by H2S, determining their safety, efficacy, and tolerance.

18.
Brachytherapy ; 23(5): 617-622, 2024.
Article in English | MEDLINE | ID: mdl-39079841

ABSTRACT

PURPOSE: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies. METHODS: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints. RESULTS: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66 mm before treatment to 12.25 ± 9.27 mm at the last follow-up (p < 0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths. CONCLUSION: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies.


Subject(s)
Brachytherapy , Iodine Radioisotopes , Lymphatic Metastasis , Palliative Care , Tomography, X-Ray Computed , Humans , Brachytherapy/methods , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Retrospective Studies , Lymphatic Metastasis/radiotherapy , Aged , Female , Palliative Care/methods , Adult , Treatment Failure , Lymph Nodes/pathology , Aged, 80 and over , Treatment Outcome , Radiotherapy, Image-Guided/methods , Survival Rate
19.
Nitric Oxide ; 150: 18-26, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38971520

ABSTRACT

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.


Subject(s)
Hydrogen Sulfide , Skin Diseases , Hydrogen Sulfide/metabolism , Humans , Skin Diseases/drug therapy , Skin Diseases/metabolism , Animals , Skin/metabolism
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