ABSTRACT
Leguminosae exhibits a wide diversity of legume forms with varying degrees of spiral morphologies, serving as an ideal clade for studying the growth and development of spiral organs. While soybean (Glycine max) develops straight pods, the pod of the model legume Medicago truncatula is a helix structure. Despite the fascinating structures and intensive description of the pods in legumes, little is known regarding the genetic mechanism underlying the highly varied spirality of the legume pods. In this study, we found that KINASE-INDUCIBLE DOMAIN INTERACTING 8 (MtKIX8) plays a key role in regulating the pod structure and spirality in M. truncatula. Unlike the coiled and barrel-shaped helix pods of the wild type, the pods of the mtkix8 mutant are loose and deformed and lose the topologic structure as observed in the wild-type pods. In the pods of the mtkix8 mutant, the cells proliferate more actively and overly expand, particularly in the ventral suture, resulting in uncoordinated growth along the dorsal and ventral sutures of pods. The core cell cycle genes CYCLIN D3s are upregulated in the mtkix8 pods, leading to the prolonged growth of the ventral suture region of the pods. Our study revealed the key role of MtKIX8 in regulating seed pod development in M. truncatula and demonstrates a genetic regulatory model underlying the establishment of the helical pod in legumes.
Subject(s)
Gene Expression Regulation, Plant , Medicago truncatula , Plant Proteins , Medicago truncatula/genetics , Medicago truncatula/growth & development , Medicago truncatula/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Mutation/genetics , Seeds/genetics , Seeds/growth & developmentABSTRACT
Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.
Subject(s)
Hydrogen Sulfide , Signal Transduction , Thiosulfates , Thiosulfates/chemistry , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/chemistry , Humans , Animals , Signal Transduction/drug effectsABSTRACT
BACKGROUND: The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult. RESULTS: We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography. CONCLUSIONS: Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.
Subject(s)
Escherichia coli , Inclusion Bodies , Escherichia coli/metabolism , Recombinant Proteins , Inclusion Bodies/metabolism , Disulfides/metabolismABSTRACT
BACKGROUND: Oxyntic gland neoplasm (OGN) is a rare subtype of gastric cancer. The aim of this study is to evaluate the prevalence, clinicopathological features, effectiveness and safety of endoscopic treatment, as well as the prognosis of OGN. METHODS: We retrospectively analyzed the data of patients pathologically diagnosed with OGN at our hospital from November 1, 2019 to May 1, 2023. RESULTS: A total of 36 patients with 45 lesions were identified, resulting in a disease frequency of 0.047% (36/76,832). The mean age was 55.0 ± 7.5 years, with a male-to-female ratio of about 1:1.12. Most lesions were ≤10 mm in size (84.4%), located in the upper third of the stomach (73.3%), exhibited slight elevation (75.5%), appeared whitish (55%), had dilated blood vessels on the surface (75.5%). 16 and 21 lesions were treated by precutting endoscopic mucosal resection (EMR-P) and endoscopic submucosal dissection (ESD), respectively. No significant differences were found between EMR-P and ESD in terms of en bloc resection rate (100% vs 100%, p = 1.000), complete resection rate (100% vs 90.5%, p = 0.495), and curative resection rate (93.8% vs 90.5%, p = 1.000). No complications such as bleeding and perforation were observed. No recurrence or metastasis was observed during the follow-up period. CONCLUSIONS: OGN is a rare tumor with unique clinical, endoscopic, and pathological characteristics. EMR-P and ESD are deemed safe and effective for treating OGNs. The relatively faster and easier EMR-P seems at least non-inferior to ESD, especially for removal of smaller OGNs. The overall prognosis is favorable.
Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Humans , Male , Female , Middle Aged , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy , Stomach Neoplasms/epidemiology , Prevalence , Aged , Treatment Outcome , Adult , Prognosis , Gastroscopy , Gastric Mucosa/pathology , Gastric Mucosa/surgery , China/epidemiologyABSTRACT
The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.
ABSTRACT
Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.
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Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.
Subject(s)
Maternal Exposure , Meconium , Particulate Matter , Humans , Female , Meconium/chemistry , Pregnancy , Cohort Studies , Infant, Newborn , Adult , Air PollutantsABSTRACT
The development of high-performance flexible pressure sensors with porous hierarchical microstructures is limited by the complex and time-consuming preparation processes of porous hierarchical microstructures. In this study, a simple modified heat curing process was first proposed to achieve one-step preparation of porous hemispherical microstructures on a polydimethylsiloxane (PDMS) substrate. In this process, a laser-prepared template was used to form surface microstructures on PDMS film. Meanwhile, the thermal decomposition of glucose monohydrate additive during heat curing of PDMS led to the formation of porous structures within PDMS film. Further, based on the obtained PDMS/CNTs electrodes with porous hemisphere array and ionic polymer dielectric layers, high-performance ionic piezocapacitive sensors were realized. Under the synergistic effect of the low-stiffness porous hemisphere microstructure and the electric double layer of the ionic polymer film, the sensor based on an ionic polymer film with a 1:0.75 ratio of P(VDF-HFP):[EMIM][TFSI] not only achieves a sensitivity of up to 106.27 kPa-1 below 3 kPa, but also has a wide measurement range of over 400 kPa, which has obvious advantages in existing flexible piezocapacitive sensors. The rapid response time of 110 s and the good stability of 2300 cycles of the sensor further elucidate its practicality. The application of the sensor in pulse monitoring, speech recognition, and detection of multiple dynamic loads verifies its excellent sensing performance. In short, the proposed heat curing process can simultaneously form porous structures and surface microstructures on PDMS films, greatly simplifying the preparation process of porous hierarchical microstructures and providing a simple and feasible way to obtain high-performance flexible pressure sensors.
ABSTRACT
OBJECTIVE: To investigate the effect of sequential distalization on increasing gaps in the maxillary anterior teeth, focusing on the control of torque and three-dimensional teeth movement during anterior retraction with clear aligners in extraction cases. METHODS: We recruited 24 patients who were undergoing extraction bilateral maxillary first premolars with clear aligners. According to a predetermined increment in the spaces between the maxillary anterior teeth, the patients were divided into three groups: those with no gap (9 cases), a 0.5 mm gap (6 cases) and a 1.0 mm gap (9 cases). In each group, a 2.0 mm en-mass retraction was applied on the anterior teeth. Plaster casts of the upper full dentition were obtained both before and after a 2 mm retraction. The palatal folds were used to overlap each pair of models. The three-dimensional movement of the teeth and the change of torque for the anterior teeth were subsequently analyzed using Geomagic Studio 2014 software. RESULTS: The change in torque in the groups with added gaps was significantly smaller than that in the group with no gaps (P < 0.05). There was no significant difference in this respect when comparing the group with a 0.5 mm gap added to the group with a 1.0 mm gap was added (P > 0.05). In the labial-lingual and vertical directions, the displacements of the central and lateral incisors were smaller in the groups with additional gaps compared to those in the groups without gaps (P < 0.05). However, there was no significant difference observed when comparing the group with a 0.5 mm added gap to the group with a 1.0 mm added gap (P > 0.05). Then, a comparison was made between the displacement of the second premolar to the second molar in the mesial-distal direction across all groups. The study revealed that the anchorage molars in the group without gaps demonstrated significantly smaller displacement compared to those in the group with additional gaps (P < 0.05). CONCLUSION: Advantages were observed in controlling the torque of the anterior teeth and achieving a desired pattern closer to normal bodily movement by sequentially distalizing the maxillary anterior teeth gaps. Increasing the gaps between the maxillary anterior teeth also resulted in improved control of the vertical direction of the anterior teeth. However, this retraction strategy necessitates substantial protection of the anchorage molars.
Subject(s)
Malocclusion , Orthodontic Appliances, Removable , Humans , Incisor , Prospective Studies , Torque , Malocclusion/prevention & control , Tooth Movement Techniques/methods , Maxilla , Finite Element AnalysisABSTRACT
Zero-dimensional (0D) hybrid metal halides have been emerged as room-temperature phosphorescence (RTP) materials, but synchronous optimization of multiple phosphorescence performance in one structural platform remains less resolved, and stable RTP activity in aqueous medium is also unrealized due to serious instability toward water and oxygen. Herein, we demonstrated a photophysical tuning strategy in a new 0D hybrid zinc halide family of (BTPP)2ZnX4 (BTPP = benzyltriphenylphosphonium, X = Cl and Br). Infrequently, the delicate combination of organic and inorganic species enables this family to display multiple ultralong green afterglow and efficient self-trapped exciton (STE) associated cyan phosphorescence. Compared with inert luminescence of [BTPP]+ cation, incorporation of anionic [ZnX4]2- effectively enhance the spin-orbit coupling effect, which significantly boosts the photoluminescence quantum yield (PLQY) up to 30.66% and 54.62% for afterglow and phosphorescence, respectively. Synchronously, the corresponding luminescence lifetime extend to 143.94 ms and 0.308 µs surpassing the indiscernible phosphorescence of [BTPP]X salt. More importantly, this halide family presents robust RTP emission with nearly unattenuated PLQY in water and harsh condition (acid and basic aqueous solution) over half a year. The highly efficient integrated afterglow and STE phosphorescence as well as ultrahigh aqueous state RTP realize multiple anti-counterfeiting applications in wide chemical environments.
ABSTRACT
As a promising gene therapy strategy, controllable small molecule-mRNA covalent modification in tumor cells could be initiated by singlet oxygen (1O2) to complete the modification process. However, in vivo generation of 1O2 is usually dependent on excitation of external light, and the limited light penetration of tissues greatly interferes the development of deep tumor phototherapy. Here, we constructed a tumor-targeting nano-micelle for the spontaneous intracellular generation of 1O2 without the need for external light, and inducing a high level of covalent modification of mRNA in tumor cells. Luminal and Ce6 were chemically bonded to produce 1O2 by chemiluminescence resonance energy transfer (CRET) triggered by high levels of hydrogen peroxide (H2O2) in the tumor microenvironment. The sufficient 1O2 oxidized the loaded furan to highly reactive dicarbonyl moiety, which underwent cycloaddition reaction with adenine (A), cytosine (C) or guanine (G) on the mRNA for interfering with the tumor cell protein expression, thereby inhibiting tumor progression. In vitro and in vivo experiments demonstrated that this self-initiated gene therapy nano-micelle could induce covalent modification of mRNA by 1O2 without external light, and the process could be monitored in real time by fluorescence imaging, which provided an effective strategy for RNA-based tumor gene therapy.
ABSTRACT
OBJECTIVES: To investigate the effect of reactive oxygen species (ROS)/silent information regulator 1 (SIRT1) on hyperoxia-induced mitochondrial injury in BEAS-2B cells. METHODS: The experiment was divided into three parts. In the first part, cells were divided into H0, H6, H12, H24, and H48 groups. In the second part, cells were divided into control group, H48 group, H48 hyperoxia+SIRT1 inhibitor group (H48+EX 527 group), and H48 hyperoxia+SIRT1 agonist group (H48+SRT1720 group). In the third part, cells were divided into control group, 48-hour hyperoxia+N-acetylcysteine group (H48+NAC group), and H48 group. The ROS kit was used to measure the level of ROS. Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins. Transmission electron microscopy was used to observe the morphology of mitochondria. RESULTS: Compared with the H0 group, the H6, H12, H24, and H48 groups had a significantly increased fluorescence intensity of ROS (P<0.05), the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins (P<0.05), and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins (P<0.05). Compared with the H48 group, the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio (P<0.05), and the H48+EX 527 group had a significant reduction in the mitochondrial area (P<0.05). Compared with the H48 group, the H48+NAC group had a significantly decreased fluorescence intensity of ROS (P<0.05) and significantly increased levels of SIRT1 protein, mitochondria-related proteins, mitochondrial area, and mitochondrial aspect ratio (P<0.05). CONCLUSIONS: The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.
Subject(s)
Bronchi , Epithelial Cells , Hyperoxia , Reactive Oxygen Species , Sirtuin 1 , Sirtuin 1/metabolism , Sirtuin 1/physiology , Sirtuin 1/genetics , Humans , Reactive Oxygen Species/metabolism , Hyperoxia/complications , Hyperoxia/metabolism , Epithelial Cells/metabolism , Bronchi/metabolism , Mitochondria/metabolism , Cells, Cultured , Cell LineABSTRACT
OBJECTIVES: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Child , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Female , Risk Factors , Child, Preschool , Retrospective Studies , Infant , Recurrence , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , East Asian PeopleABSTRACT
Utilizing panel data from 30 Chinese provinces, this research examines the non-linear relationship between regional environmental, social, and governance (ESG) performance and carbon emissions (CE) from the viewpoint of green credit. The study reveals a single threshold effect between ESG performance and CE, with green credit acting as the threshold variable. When the amount of green credit in a region exceeds the threshold, the growth rate of CE in that region begins to decline with higher ESG scores. Furthermore, green credit acts as a catalyst, playing a negative moderating role between ESG performance and CE, validated by both threshold regression and fixed effects models on panel data. Green credit indirectly influences carbon emissions by supporting green innovation, thus facilitating the transition to a greener economic development framework. Lastly, regional disparities are found in the moderating influence of green credit between ESG performance and CE. In regions with high ESG performance, the moderating impact of green credit is smaller, while in regions with low ESG performance, the effect is more significant. The research findings offer theoretical backing for policymakers regarding the efficacy of ESG in achieving carbon neutrality objectives, and offer valuable strategic recommendations for the diversified formulation of green credit strategies on both national and provincial scales. Regional heterogeneity test results provide valuable support for formulating policies that encourage green credit in provinces with low ESG performance.
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Pesticide overuse has been an increasing concern in China. Digital technology, such as smartphone access, is considered an effective way to promote proper use of pesticides. Using the Chinese Extended Family Database (2015, 2017, and 2019), this study empirically examines the impact of smartphone access on pesticide use intensity among Chinese farmers. The results show a "double-edged sword" effect of smartphone access on pesticide use intensity. In rural areas with a low level of digital economy, greater smartphone access led to higher pesticide use intensity. In rural areas with a high digital economy level, smartphone access reduced pesticide use intensity. The study results show that reducing pesticide use intensity through digital technology is not a linear process but a complicated one that involves social and engineering integration, including an increase in access to smartphones, development of a regional digital economy, reconstruction of agricultural extension systems, and enhancement of the capacity of digital technology.
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In diabetes, pancreatic ß-cells gradually lose their ability to secrete insulin with disease progression. ß-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by ß-cell dedifferentiation and identified in diabetic animals, has attracted attention as an underlying molecular mechanism of ß-cell dysfunction. Previously, we reported ß-cell dedifferentiation suppression by calorie restriction, not by reducing hyperglycemia using hypoglycemic agents (including sodium-glucose cotransporter inhibitors), in an obese diabetic mice model (db/db). Here, to explore further mechanisms of the effects of food intake on ß-cell function, db/db mice were fed either a high-carbohydrate/low-fat diet (db-HC) or a low-carbohydrate/high-fat diet (db-HF) using similar calorie restriction regimens. After one month of intervention, body weight reduced, and glucose intolerance improved to a similar extent in the db-HC and db-HF groups. However, ß-cell dedifferentiation did not improve in the db-HC group, and ß-cell mass compensatory increase occurred in this group. More prominent fat accumulation occurred in the db-HC group livers. The expression levels of genes related to lipid metabolism, mainly regulated by peroxisome proliferator-activated receptor α and γ, differed significantly between groups. In conclusion, the fat/carbohydrate ratio in food during calorie restriction in obese mice affected both liver lipid metabolism and ß-cell dedifferentiation.
Subject(s)
Caloric Restriction , Diabetes Mellitus, Experimental , Animals , Mice , Mice, Obese , Diet, High-Fat/adverse effects , Cell Dedifferentiation , Diet, Carbohydrate-Restricted , Liver , Carbohydrates , ObesityABSTRACT
Pancreatitis and pancreatic cancer (PC) stand as the most worrisome ailments affecting the pancreas. Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases, yet their true nature continues to elude their grasp. Within this realm, oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC. Excessive accumulation of reactive oxygen species (ROS) can cause oxidative stress, and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides (NOX). NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells, activate pancreatic stellate cells, and mediate macrophage polarization. Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis, creating an oxidative microenvironment that can cause abnormal apoptosis, epithelial to mesenchymal transition and genomic instability. Therefore, understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases. In this review, we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders, aiming to provide novel insights into understanding the mechanisms underlying these diseases.
Subject(s)
Epithelial-Mesenchymal Transition , Pancreatitis , Humans , Reactive Oxygen Species , NADP , NADPH Oxidases/metabolism , Oxidative StressABSTRACT
In this editorial, we commented on the article published in the recent issue of the World Journal of Diabetes. Diabetic cardiomyopathy (DCM) is characterized by myocardial fibrosis, ventricular hypertrophy and diastolic dysfunction in diabetic patients, which can cause heart failure and threaten the life of patients. The pathogenesis of DCM has not been fully clarified, and it may involve oxidative stress, inflammatory stimulation, apoptosis, and autophagy. There is lack of effective therapies for DCM in the clinical practice. Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques, and exhibit definite cardiovascular protective effects. Studies have shown that statins also have anti-inflammatory and antioxidant effects. We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and anti-inflammatory effects of macrophage polarization on diabetic myocardium, and thereby improving DCM.
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BACKGROUND: Gastric cancer has been traditionally treated with chemotherapy as the primary mode of treatment. However, recent studies have shown that chemoimmunotherapy is also effective and, in some cases, better than chemotherapy treatment. Current study aimed to find the efficacy of chemoimmunotherapy versus chemotherapy in the treatment of gastric cancer. METHODS: Using electronic databases, including PubMed, Embase, and EBSCO, a thorough literature search was carried out for the years 2006 to 2023. The search strategy was designed to identify relevant studies based on chemoimmunotherapy and chemotherapy intervention, and the search was conducted using appropriate keywords and MeSH terms. The retrieved studies were screened for relevance based on their titles, abstracts, and full texts. The studies' inclusion criteria were predefined, and the selected studies were then subjected to a quality assessment using GradePro GDT. The data from selected studies were extracted and analyzed using Revman version 5.4. RESULTS: The study found that chemoimmunotherapy treatment resulted in a significant improvement in overall survival (OS) with a risk ratio (RR) of 1.54 and a 95% Confidence Interval (CI) of 1.25 to 1.89. The overall effect was also found to be significant, with a p-value of less than 0.001. Furthermore, we also observed an improvement in the 1-year, 3-year, and 5-year survival rates with risk ratio (RR) of 1.09 (95% CI: 1.01, 1.17), 1.43 (95% CI: 1.28, 1.60), and 1.59 (95% CI: 1.10, 2.30), respectively. In addition, it's also found that chemoimmunotherapy treatment also resulted in an improvement in DFS with an RR of 1.94 and a 95% CI of 1.44 to 2.59. Overall, these results suggest that chemoimmunotherapy treatment can be an effective approach in comparison to chemotherapy for improving overall survival and disease-free survival in the studied population. CONCLUSION: This study comparing chemoimmunotherapy versus chemotherapy for gastric cancer showed that both treatments were effective, but chemoimmunotherapy had more significant efficacy. To support these results, additional studies with a large sample size and a longer follow-up time are required.
Subject(s)
Immunotherapy , Stomach Neoplasms , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/therapyABSTRACT
BACKGROUND: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare condition with significant psychological implications. However, our understanding of its impact on postoperative sexual function and mental health is still limited. AIM: Evaluate the mental health status and sexual functioning of women with MRKH syndrome after vaginoplasty surgery. METHODS: We enrolled 53 cases with MRKH syndrome who underwent artificial vaginoplasty. The participants were asked to participate in a two-round survey conducted between February 2021 during the covid-19 period and March 2023. The survey included questionnaires to measure depression, anxiety, self-esteem, and sexual functioning. Differences between scores over time were analysed using a paired sample t-test, and we assessed the correlation between mental health and sexual functioning. RESULTS: In the first round, patients' mean ± SD age at surgery was 23.6 ± 4.5 years old, and the mean ± SD time that had elapsed since surgery at the time of the survey was 34.2 ± 20.8 months. None of the patients reported low self-esteem, 45.3 % reported mild-to-moderate depression, and 34.0 % reported mild anxiety. Thirty patients have had vaginal intercourse during the last six months. The mean ± SD Female Sexual Functioning Index score was 24.6 ± 4.4, and 60.0 % had a score of 23.5 or higher, indicating high sexual functioning. The sexual functioning scores were positively correlated with self-esteem scores and negatively correlated with depression or anxiety scores (p < 0.05). There was no significant improvement in patient's mental health status and sexual function between the second round survey (71.3 ± 17.8 months after surgery) and the first round survey (p > 0.05). In contrast, the sexual arousal of FSFI were significantly higher in the second survey round (p < 0.05). CONCLUSION: Most patients undergoing vaginoplasty reported persisting mental health challenges. However, the majority reported good sexual functioning.