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1.
Cancer Res ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39163511

ABSTRACT

Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.

2.
Anal Chem ; 96(32): 13260-13269, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39087711

ABSTRACT

The occurrence and development of diseases are accompanied by abnormal activity or concentration of biomarkers in cells, tissues, and blood. However, the insufficient sensitivity and accuracy of the available fluorescence probes hinder the precise monitoring of associated indexes in biological systems, which is generally due to the high probe intrinsic fluorescence and false-negative signal caused by the reactive oxygen species (ROS)-induced probe decomposition. To resolve these problems, we have engineered a ROS-stable, meso-carboxylate boron dipyrromethene (BODIPY)-based fluorescent probe, which displays quite a low background fluorescence due to the doubly quenched intrinsic fluorescence by a combined strategy of the photoinduced electron transfer (PET) effect and "ester-to-carboxylate" conversion. The probe achieved a high S/N ratio with ultrasensitivity and good selectivity toward biothiols, endowing its fast detection capability toward the biothiol level in 200×-diluted plasma samples. Using this probe, we achieved remarkable distinguishing of liver injury plasma from normal plasma even at 80× dilution. Moreover, owing to its good stability toward ROS, the probe was successfully employed for high-fidelity imaging of the negative fluctuation of the biothiol level in nonsmall-cell lung cancer (NSCLC) during dihydroartemisinin-induced ferroptosis. This delicate design of suppressing intrinsic fluorescence reveals insights into enhancing the sensitivity and accuracy of fluorescent probes toward the detection and imaging of biomarkers in the occurrence and development of diseases.


Subject(s)
Artemisinins , Boron Compounds , Ferroptosis , Fluorescent Dyes , Fluorescent Dyes/chemistry , Humans , Artemisinins/pharmacology , Artemisinins/chemistry , Boron Compounds/chemistry , Ferroptosis/drug effects , Animals , Mice , Sulfhydryl Compounds/chemistry , Optical Imaging , Reactive Oxygen Species/metabolism
3.
Anal Chem ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014519

ABSTRACT

Liver injury significantly affects a patient's health and quality of life. However, timely and convenient diagnosis of this disease via whole blood detection remains challenging due to the lack of user-friendly and fast readout blood test methods. Herein, we developed such a method for the swift auxiliary diagnosis of liver injury via whole blood detection using a customed point-of-care testing (POCT) system consisting of a biothiols-activatable chemiluminescent probe and a hand-held POCT device. Biothiols served as the target to build the activable chemiluminescence probe due to their abnormal level in liver injury. Compared with fluorescent and electrical POCTs, this method is more convenient and has strong universality. By incorporating cyclodextrin via host-guest chemistry, we intensified chemiluminescence while mitigating chemical hemolysis caused by the dissolution of organic molecules, making this system suitable for whole blood analysis. Preliminary assessments in aqueous solutions, living cells, and mouse models confirmed its sensitivity, reliability, and feasibility. Simply mixing blood with the probe for 30 min yielded a clear signal readout within 15 s on the POCT device. Utilizing this portable detector, the reduced biothiol level was tested in 18 liver injury patient blood samples, and the results were similar to those measured by a commercial kit and in vivo imaging system. Thus, this work provides a universal platform for the fast and convenient detection of other biomarkers in whole blood samples and opens up possibilities for the rapid clinical diagnosis of diseases, enabling patients to conduct home self-examinations with ease.

4.
Cytokine ; 181: 156691, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986253

ABSTRACT

BACKGROUND: The interleukin-17 (IL-17) signaling pathway is intricately linked with immunity and inflammation; however, the association between the IL-17 signaling pathway and skeletal muscle inflammation remains poorly understood. The study aims to investigate the role of the IL-17 signaling pathway in skeletal muscle inflammation and to evaluate the therapeutic potential of anti-IL-17 antibodies in reducing muscle inflammation. METHODS: A skeletal muscle inflammation model was induced by cardiotoxin (CTX) injection in C57BL6/J mice. Following treatment with an anti-IL-17 antibody, we conducted a comprehensive analysis integrating single-cell RNA sequencing (scRNA-seq), bioinformatics, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blot techniques to elucidate underlying mechanisms. RESULTS: scRNA-seq analysis revealed a significant increase in neutrophil numbers and activity in inflamed skeletal muscle compared to other cell types, including macrophages, T cells, B cells, endothelial cells, fast muscle cells, fibroblasts, and skeletal muscle satellite cells. The top 30 differentially expressed genes within neutrophils, along with 55 chemokines, were predominantly enriched in the IL-17 signaling pathway. Moreover, the IL-17 signaling pathway exhibited heightened expression in inflamed skeletal muscle, particularly within neutrophils. Treatment with anti-IL-17 antibody resulted in the suppression of IL-17 signaling pathway expression, accompanied by reduced levels of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, as well as decreased numbers and activity of Ly6g+/Mpo+ neutrophils compared to CTX-induced skeletal muscle inflammation. CONCLUSION: Our findings suggest that the IL-17 signaling pathway plays a crucial role in promoting inflammation within skeletal muscle. Targeting this pathway may hold promise as a therapeutic strategy for ameliorating the inflammatory micro-environment and reducing cytokine production.


Subject(s)
Inflammation , Interleukin-17 , Mice, Inbred C57BL , Muscle, Skeletal , Signal Transduction , Animals , Signal Transduction/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Mice , Interleukin-17/metabolism , Inflammation/metabolism , Inflammation/pathology , Male , Neutrophils/metabolism , Neutrophils/immunology , Myositis/metabolism , Myositis/drug therapy , Myositis/immunology
5.
Sci Rep ; 14(1): 16072, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992076

ABSTRACT

Aiming at the problem of zero sequence voltage generated by unbalance parameters of line to ground, which affects arc suppression effect of grounding fault of controllable voltage source. By analyzing the influence of ground unbalance parameters on the arc suppression effect of controllable voltage source under different grounding modes, the mechanism of full compensation arc suppression based on zero sequence voltage of neutral point is revealed, and on this basis, a fully compensated arc suppression model of controllable voltage source controlled by double closed loop PI is established, and the deviation control is carried out by using the neutral voltage of distribution network and the voltage of fault phase supply. The residual voltage ring adopts the ground fault phase residual voltage for closed loop control. The simulation results show that the dual-closed-loop PI control algorithm can continuously stabilize the output waveform of the controllable voltage source. When the transition resistance is 0.1 ~ 10 kΩ, the residual voltage stabilization time of the independent controllable voltage source grounding method is 43 ms ~ 2.4 s, and the parallel arc suppression coil grounding method is 43 ms ~ 4.7 s. The proposed dual closed-loop PI control method for neutral point voltage deviation and fault residual voltage can stabilize the residual voltage of the grounded fault phase to below 10 V, forcing reliable arc extinction at the grounded fault point, exhibiting good stability. Low-voltage simulation tests have also proved the feasibility of the algorithm.

6.
J Orthop Surg Res ; 19(1): 366, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902778

ABSTRACT

BACKGROUND: In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells (AD-MSC), or umbilical cord-derived mesenchymal stem cells (UC-MSC) have shown promise in alleviating symptoms. However, which types of mesenchymal stem cells (MSCs) have the best therapeutic outcomes remain uncertain. METHOD: We systematically searched PubMed, OVID, Web of Science, and the Cochrane Library until January 1, 2024. The study evaluated five endpoints: Visual Analog Score (VAS) for Pain, Range of Motion (ROM), Whole-Organ Magnetic Resonance Imaging Score (WORMS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and adverse events (ADs). Standard meta-analysis and network meta-analysis were performed using Stata 16.0. RESULTS: Fifteen studies involving 585 patients were included in the meta-analysis. Standard meta-analysis revealed significant improvements with MSCs in VAS score (P < 0.001), knee ROM (P < 0.001), and WOMAC (P < 0.016) compared to traditional therapy. In the network meta-analysis, autologous MSCs significantly improved VAS score [SMD = 2.94, 95% CI (1.90, 4.56)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to traditional therapy. Similarly, BM-MSC significantly improved VAS score [SMD = 0.31, 95% CI (0.11, 0.91)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to hyaluronic acid. However, compared with traditional therapy, autologous or allogeneic MSCs were associated with more adverse reactions [SMD = 0.11, 95% CI (0.02, 0.59)], [SMD = 0.13, 95% CI (0.002, 0.72)]. Based on the surface under the cumulative ranking results, autologous BM-MSC showed the most improvement in ROM and pain relief in KOA patients, UC-MSC (SUCRA 94.1%) were most effective for positive WORMS, and AD-MSC (SUCRA 70.6%) were most effective for WOMAC-positive patients. CONCLUSION: MSCs transplantation effectively treats KOA patients, with autologous BM-MSC potentially offering more excellent benefits.


Subject(s)
Mesenchymal Stem Cell Transplantation , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Mesenchymal Stem Cell Transplantation/methods , Treatment Outcome , Network Meta-Analysis , Mesenchymal Stem Cells , Adipose Tissue/cytology , Range of Motion, Articular , Umbilical Cord/cytology , Transplantation, Autologous/methods , Male , Female , Middle Aged , Pain Measurement
7.
Anal Chem ; 96(18): 7248-7256, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38655839

ABSTRACT

Ferroptosis modulation is a powerful therapeutic option for pancreatic ductal adenocarcinoma (PDAC) with a low 5-year survival rate and lack of effective treatment methods. However, due to the dual role of ferroptosis in promoting and inhibiting pancreatic tumorigenesis, regulating the degree of ferroptosis is very important to obtain the best therapeutic effect of PDAC. Biothiols are suitable as biomarkers of imaging ferroptosis due to the dramatic decreases of biothiol levels in ferroptosis caused by the inhibited synthesis pathway of glutathione (GSH) and the depletion of biothiol by reactive oxygen species. Moreover, a very recent study reported that cysteine (Cys) depletion can lead to pancreatic tumor ferroptosis in mice and may be employed as an effective therapeutic strategy for PDAC. Therefore, visualization of biothiols in ferroptosis of PDAC will be helpful for regulating the degree of ferroptosis, understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis, and further promoting the study and treatment of PDAC. Herein, two biothiol-activable near-infrared (NIR) fluorescent/photoacoustic bimodal imaging probes (HYD-BX and HYD-DX) for imaging of pancreatic tumor ferroptosis were reported. These two probes show excellent bimodal response performances for biothiols in solution, cells, and tumors. Subsequently, they have been employed successfully for real-time visualization of changes in concentration levels of biothiols during the ferroptosis process in PDAC cells and HepG2 cells. Most importantly, they have been further applied for bimodal imaging of ferroptosis in pancreatic cancer in mice, with satisfactory results. The development of these two probes provides new tools for monitoring changes in concentration levels of biothiols in ferroptosis and will have a positive impact on understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis and further promoting the study and treatment of PDAC.


Subject(s)
Ferroptosis , Fluorescent Dyes , Optical Imaging , Pancreatic Neoplasms , Photoacoustic Techniques , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Humans , Fluorescent Dyes/chemistry , Animals , Mice , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/metabolism , Infrared Rays , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology
8.
Anal Chem ; 96(10): 4103-4110, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38427614

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5 year survival rate less than 12%. This malignancy is closely related to the unique tumor microenvironment (TME), which is characterized by a hypovascular and hyperdense extracellular matrix, making it difficult for drugs to permeate the tumor center. Near-infrared fluorescence (NIRF) imaging, which has high sensitivity and resolution, may improve the survival rate of PDAC patients. In this study, we first used JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazine-1-yl] diazene-1-ium-1,2-diolate) to specifically dilate blood vessels within the TME of PDAC patients and subsequently injected IR820-PEG-MNPs (IPM NPs) to diagnose and treat orthotopic PDAC. We found that JS-K promoted the accumulation of IPM NPs in orthotopic Pan02 tumor-bearing mice and was able to increase the tumor signal-to-background ratio (SBR) in the orthotopic PDAC area by 41.5%. In addition, surgical navigation in orthotopic Pan02 tumor-bearing mice and complete tumor resection based on fluorescence imaging were achieved with a detection sensitivity of 81.0%. Moreover, we verified the feasibility of the combination of laparoscopy and photothermal ablation (PTA) for the treatment of PDAC. Finally, we demonstrated that IPM NPs had greater affinity for human PDAC tissues than for normal pancreatic tissues ex vivo, preliminarily highlighting the potential for clinical translation of these NPs. In conclusion, we developed and validated a novel sequential delivery strategy that promotes the accumulation of nanoagents in the tumor area and can be used for the diagnosis and treatment of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Mice , Animals , Melanins , Precision Medicine , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/drug therapy , Optical Imaging/methods , Cell Line, Tumor , Tumor Microenvironment
9.
Chem Asian J ; 19(9): e202400052, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38436107

ABSTRACT

Aminopeptidases, enzymes with critical roles in human body, are emerging as vital biomarkers for metabolic processes and diseases. Aberrant aminopeptidase levels are often associated with diseases, particularly cancer. Small-molecule probes, such as fluorescent, fluorescent/photoacoustics, bioluminescent, and chemiluminescent probes, are essential tools in the study of aminopeptidases-related diseases. The fluorescent probes provide real-time insights into protein activities, offering high sensitivity in specific locations, and precise spatiotemporal results. Additionally, photoacoustic probes offer signals that are able to penetrate deeper tissues. Bioluminescent and chemiluminescent probes can enhance in vivo imaging abilities by reducing the background. This comprehensive review is focused on small-molecule probes that respond to four key aminopeptidases: aminopeptidase N, leucine aminopeptidase, Pyroglutamate aminopeptidase 1, and Prolyl Aminopeptidase, and their utilization in imaging tumors and afflicted regions. In this review, the design strategy of small-molecule probes, the variety of designs from previous studies, and the opportunities of future bioimaging applications are discussed, serving as a roadmap for future research, sparking innovations in aminopeptidase-responsive probe development, and enhancing our understanding of these enzymes in disease diagnostics and treatment.


Subject(s)
Aminopeptidases , Fluorescent Dyes , Humans , Aminopeptidases/metabolism , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Molecular Probes/chemistry , Optical Imaging , Animals , Small Molecule Libraries/chemistry , Small Molecule Libraries/chemical synthesis , Neoplasms/diagnostic imaging
10.
Adv Biol (Weinh) ; 8(4): e2300558, 2024 04.
Article in English | MEDLINE | ID: mdl-38329214

ABSTRACT

Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle-atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC-Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC-Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single-cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor ß1 (TGF-ß1)-Smad3-Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC-Exo intervention inhibited the TGF-ß1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC-Exo-based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF-ß1/Smad3 pathway.


Subject(s)
Exosomes , Satellite Cells, Skeletal Muscle , Humans , Rats , Animals , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Satellite Cells, Skeletal Muscle/metabolism , Exosomes/metabolism , Rats, Sprague-Dawley , Muscular Atrophy/genetics , Muscular Atrophy/metabolism , Muscular Atrophy/therapy , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Fibrosis
11.
Colloids Surf B Biointerfaces ; 236: 113799, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38367290

ABSTRACT

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.


Subject(s)
Colitis , Inflammatory Bowel Diseases , Mice , Animals , Telmisartan/pharmacology , Telmisartan/metabolism , Hydrogels/pharmacology , Intestinal Mucosa/metabolism , Tight Junctions/metabolism , Tight Junctions/pathology , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/pathology , Colitis/pathology , Colon/metabolism , Inflammation/metabolism , Dextran Sulfate/metabolism , Disease Models, Animal , Mice, Inbred C57BL
12.
J Environ Manage ; 352: 120051, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38262282

ABSTRACT

With the rapid growth of the metallurgical industry, there is a significant increase in the production of metallurgical slags. The waste slags pose significant challenges for their disposal because of complex compositions, low utilization rates, and environmental toxicity. One promising approach is to utilize metallurgical slags as catalysts for treatment of refractory organic pollutants in wastewater through advanced oxidation processes (AOPs), achieving the objective of "treating waste with waste". This work provides a literature review of the source, production, and chemical composition of metallurgical slags, including steel slag, copper slag, electrolytic manganese residue, and red mud. It emphasizes the modification methods of metallurgical slags as catalysts and the application in AOPs for degradation of refractory organic pollutants. The reaction conditions, catalytic performance, and degradation mechanisms of organic pollutants using metallurgical slags are summarized. Studies have proved the feasibility of using metallurgical slags as catalysts for removing various pollutants by AOPs. The catalytic performance was significantly influenced by slags-derived catalysts, catalyst modification, and process factors. Future research should focus on addressing the safety and stability of catalysts, developing green and efficient modification methods, enhancing degradation efficiency, and implementing large-scale treatment of real wastewater. This work offers insights into the resource utilization of metallurgical slags and pollutant degradation in wastewater.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Wastewater , Copper , Hazardous Substances , Metallurgy , Oxidation-Reduction , Water Pollutants, Chemical/analysis
13.
Anal Chem ; 95(37): 14043-14051, 2023 09 19.
Article in English | MEDLINE | ID: mdl-37677104

ABSTRACT

Glutathione (GSH), the most abundant nonprotein biothiol, is a significant endogenous molecule that plays a key role in redox equilibrium in vivo and is regarded as a critical biomarker of cancer. Currently, various fluorescent probes have been designed and synthesized for imaging GSH at the cellular level in the visible range and the first near-infrared window (NIR-I, 750-900 nm). However, the application of these fluorescent probes for bioimaging and biosensing in vivo has been extremely hindered by the high biobackground and low tissue penetration. Herein, based on the self-assembly and disassembly of J-aggregation, we designed and synthesized a GSH-activatable probe MC-PSE for second near-infrared window (NIR-II) fluorescence and ratiometric photoacoustic imaging of GSH in vivo. The anionic cyanine-based MC-PSE tends to form stable J-aggregates in an aqueous solution. Upon the reaction with GSH, the J-aggregates of MC-PSE disassembled, the emission peak intensity of MC-PSE at 940 nm significantly increased by about 20 times, and the PA900/PA980 ratio increased by 4 times within 15 min in vitro. Notably, we used MC-PSE to visualize GSH in tumor-bearing mice and to distinguish normal and tumor areas successfully by virtue of NIR-II FL and PA dual-modal imaging. The design strategy of MC-PSE provides a novel method for ratiometric photoacoustic imaging, and MC-PSE is expected to be a powerful tool for the accurate detection of GSH in cancer diagnosis.


Subject(s)
Photoacoustic Techniques , Quinolines , Animals , Mice , Fluorescent Dyes , Diagnostic Imaging , Glutathione
14.
Theranostics ; 13(13): 4469-4481, 2023.
Article in English | MEDLINE | ID: mdl-37649601

ABSTRACT

Rationale: Pancreatic cancer, comprising mostly pancreatic ductal adenocarcinoma (PDAC), is a highly malignant disease, typically known as a hypoxic tumor microenvironment. The application of PDT in pancreatic cancer in clinic is still hampered by several shortcomings, including the (i) deep location of pancreatic cancer, (ii) tissue damage induced by optical fibers, (iii) hypoxic microenvironment, (iv) short excitation wavelengths of traditional photosensitizers, and (v) poor delivery efficiency of photosensitizers. Methods: We designed an organic nanoparticle as photosensitizer for near-infrared II (NIR-II) fluorescent (FL) imaging that exerts a type I PDT effect on deep orthotopic pancreatic tumors under excitation by a NIR (808 nm) laser. Results: This novel photosensitizer exhibits enhanced accumulation in orthotopic pancreatic cancer in mice and could be used to effectively detect pancreatic cancer and guide subsequent laser irradiation for accurate PDT of deep pancreatic cancer. In addition, we built an endoscopic platform monitored by NIR-II FL imaging to achieve minimally invasive endoscopically guided interventional photodynamic therapy (EG-iPDT) with efficient inhibition of orthotopic pancreatic cancer, which prolonged overall survival up to 78 days compared to PBS + EG-iPDT group (*p < 0.05) in a mouse model. Conclusions: Minimally invasive EG-iPDT has promise as an intraoperative treatment for early-stage or unresectable or metastatic pancreatic cancer.


Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Fluorescent Dyes/chemistry , Pancreatic Ducts/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/therapy , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/therapy , Endoscopes, Gastrointestinal , Photochemotherapy , Photosensitizing Agents , Nanoparticles , Animals , Mice
15.
Medicine (Baltimore) ; 102(29): e34256, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37478277

ABSTRACT

BACKGROUND: Peripheral nerve injuries (PNI) resulting from trauma can be severe and permanently disabling, approximately one-third of PNIs demonstrate incomplete recovery and poor functional restoration. However, despite extensive research on this aspect, complete functional recovery remains a challenge. In East Asian countries, Chinese herbal Buyang Huanwu Decoction (BHD) has been used to treat PNI for more than 200 years, and the studies of BHD to treat PNI have been increasing in recent years based on positive clinical outcomes. The purpose of this meta-analysis was to scientifically evaluate the safety and clinical efficacy of BHD in patients with PNI. METHOD: A literature search was conducted on PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, VIP, and Sinomed databases for randomized controlled clinical trials that evaluated the safety and effects of BHD alone or combination treatment on PNI. RESULTS: A total of 14 studies involving 1415 participants were included in this study. Each trial did not show significant heterogeneity or publication bias. The results showed that significant improvements of the total clinical effective rate (odds ratio = 3.55; 95% confidence interval [CI] = [2.62, 4.81]; P < .0001), radial nerve function score (standardized mean difference [SMD] = 1.28; 95% CI = [1.09, 1.47]; P = .007), motor nerve conduction velocity (SMD = 1.59; 95% CI = [1.40, 1.78]; P < .0001), sensory nerve conduction velocity (SMD = 1.69; 95% CI = [1.34, 2.05]; P < .0001), and electromyography amplitude (SMD = 2.67; 95% CI = [1.27, 4.06]; P = .0002), and significantly reduce of the visual analog scale scores (SMD = -3.85; 95% CI = [-7.55, -0.15]; P = .04) in the BHD group compared with the control group. In addition, there were no serious and permanent adverse effects in the 2 groups, the difference was not significant (odds ratio = 1.00; 95% CI = [0.40, 2.50]; P = 1.00). CONCLUSION: Current evidence suggests that BHD is an effective and safe treatment for PNI and could be treated as a complementary and alternative option with few side effects compared to a single treatment with neurotrophic drugs or electrical stimulation. However, considering the low methodological quality of the included studies, further rigorous studies are required.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal , Peripheral Nerve Injuries , Humans , Drugs, Chinese Herbal/therapeutic use , Peripheral Nerve Injuries/drug therapy , Randomized Controlled Trials as Topic , Medicine, Chinese Traditional/methods
16.
Environ Res ; 234: 116534, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37399983

ABSTRACT

Heterogeneous advanced oxidation process has been widely studied as an effective method for removing organic pollutants in wastewater, but the development of efficient catalysts is still challenging. This review summaries the present status of researches on biochar/layered double hydroxides composites (BLDHCs) as catalysts for treatment of organic wastewater. The synthesis methods of layered double hydroxides, the characterizations of BLDHCs, the impacts of process factors influencing catalytic performance, and research advances in various advanced oxidation processes are discussed in this work. The integration of layered double hydroxides and biochar provides synthetic effects for improving pollutant removal. The enhanced pollutant degradation in heterogeneous Fenton, sulfate radical-based, sono-assisted, and photo-assisted processes using BLDHCs have been verified. Pollutant degradation in heterogeneous advanced oxidation processes using BLDHCs is influenced by process factors such as catalyst dosage, oxidant addition, solution pH, reaction time, temperature, and co-existing substances. BLDHCs are promising catalysts due to the unique features including easy preparation, distinct structure, adjustable metal ions, and high stability. Currently, catalytic degradation of organic pollutants using BLDHCs is still in its infancy. More researches should be conducted on the controllable synthesis of BLDHCs, the in-depth understanding of catalytic mechanism, the improvement of catalytic performance, and large-scale application of treating real wastewater.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Wastewater , Water Pollutants, Chemical/analysis , Hydroxides , Oxidation-Reduction
17.
Chemosphere ; 337: 139404, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37399998

ABSTRACT

The release of untreated wastewater into water bodies has become a significant environmental concern, resulting in the accumulation of refractory organic pollutants that pose risks to human health and ecosystems. Wastewater treatment methods, including biological, physical, and chemical techniques, have limitations in achieving complete removal of the refractory pollutants. Chemical methods, particularly advanced oxidation processes (AOPs), have gained special attention for their strong oxidation capacity and minimal secondary pollution. Among the various catalysts used in AOPs, natural minerals offer distinct advantages, such as low cost, abundant resources, and environmental friendliness. Currently, the utilization of natural minerals as catalysts in AOPs lacks thorough investigation and review. This work addresses the need for a comprehensive review of natural minerals as catalysts in AOPs. The structural characteristics and catalytic performance of different natural minerals are discussed, emphasizing their specific roles in AOPs. Furthermore, the review analyzes the influence of process factors, including catalyst dosage, oxidant addition, pH value, and temperature, on the catalytic performance of natural minerals. Strategies for enhancing the catalytic efficiency of AOPs mediated by natural minerals are explored, mainly including physical fields, reductant addition, and cocatalyst utilization. The review also examines the practical application prospects and main challenges associated with the use of natural minerals as heterogeneous catalysts in AOPs. This work contributes to the development of sustainable and efficient approaches for organic pollutant degradation in wastewater.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Water Purification , Humans , Wastewater , Water Pollutants, Chemical/analysis , Ecosystem , Minerals/chemistry , Oxidation-Reduction
18.
Ann Anat ; 249: 152111, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37247761

ABSTRACT

BACKGROUND: With periodontal disease having an increasing incidence, mandibular free-end edentulism caused by periodontitis is clinically more common. Finite element analysis and clinical case reports were used to evaluate the influence of different designs on the load distribution of implant prosthesis in mandibular posterior free-end edentulism. METHOD: A finite element model of a mandible with posterior free-end edentulism was established. Considering the implant position and selection of single crown repair or splint repair, four designs were conducted including model A: 3435 × 37(four-unit fixed bridge supported by three implants, implant positions were 34, 35, 37); model B: 34,35 × 37, (34: a single implant crown) (35 ×37: three-unit fixed bridge supported by two implants, implant positions were 35, 37); model C: 34 × 3637(four-unit fixed bridge supported by three implants, implant positions were 34, 36, 37); and model D: 34 × 36, 37(37: a single implant crown)(34 ×36: three-unit fixed bridge supported by two implants, implant positions were 34, 36). Stress distribution and the Von Mises stress value of the implants, the crown and the bone around the implants were analyzed at vertical and 45° inclined load. RESULTS: Stress in the cortical bone was mainly concentrated around the implant neck, and maximum Von Mises stress (MVMS) of the four models was 11.6-16.1 MPa at vertical load and 61.74-96.49 MPa at 45° inclined load. Stress in the cancellous bone was concentrated around the implant base, and MVMS of four models was 3.075-3.899 MPa at vertical load and 5.021-6.165 MPa at 45° inclined load. Stress of the restoration crowns was mainly concentrated in the connector of the bridge, and MVMS of four models was 23.38-26.28 MPa at vertical load and 53.14-56.35 MPa at 45° inclined load. Stress of the implant interface was mainly concentrated on the surface of the smaller implants near the bridge, and MVMS of four models was 21.12-33.25 MPa at vertical load and 83.73-138.7 MPa at 45° inclined load. CONCLUSION: There was favorable stress distribution of the four models at vertical load and 45° inclined load. Design of a three-unit fixed bridge combined with a partial crown may be an available option for devising patient treatment plans with mandibular free-end edentulism.


Subject(s)
Dental Implants , Mandible , Humans , Finite Element Analysis , Stress, Mechanical , Bicuspid , Mandible/surgery , Denture, Partial, Fixed , Dental Stress Analysis , Dental Prosthesis, Implant-Supported , Dental Prosthesis Design
19.
Chem Asian J ; 18(13): e202300310, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37154258

ABSTRACT

Metal-complex-based materials for lithium storage have attracted great interest due to their highly designable structures with multiple active sites and well-defined lithium transport pathways. Their cycling and rate performances, however, are still constrained by structural stability and electrical conductivity. Herein, we present two hydrogen-bonded complex-based frameworks with excellent lithium storage capability. Multiple hydrogen bonds among the mononuclear molecules result in three-dimensional frameworks that are stable in electrolyte. The origin of the remarkable lithium storage performance of this family was revealed through kinetic analysis and DFT calculations.

20.
Sci Total Environ ; 884: 163835, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37137375

ABSTRACT

The biodegradability of soil organic carbon (BSOC), defined as soil mineralization C per unit of soil organic carbon (SOC), is considered to be an important indicator of SOC stability and is closely related to the global C cycle. However, the magnitude and driving mechanism of BSOC in farmland remain largely unexplored, especially at the regional scale. Here, we conducted regional scale sampling to investigate latitude distribution pattern of BSOC and the relative contributions of biotic (soil micro-food web) and abiotic (climate and soil) drivers to BSOC in the black soil region of Northeast China. Results showed that BSOC declined with increasing latitude, which indicates that as the latitude increases, SOC becomes more stable in the black soil region of Northeast China. Over a range of latitude from 43°N to 49°N, BSOC was negatively correlated with soil micro-food web metrics of diversity (indicated by species richness), biomass and connectance, and soil factors of soil pH and clay content (CC), while it was positively correlated with climate factors of mean annual temperature (MAT), mean annual precipitation (MAP) and soil factor of soil bulk density (SBD). Among those predictors, soil micro-food web metrics were the most direct factors contributing to the variations of BSOC, which exerted the largest total effect on BSOC (-0.809). Collectively, our results provide convincing evidence that soil micro-food web metrics play a direct vital role in determining the distribution pattern of BSOC over a range of latitudes in the black soil region of Northeast China. This highlights the necessity of considering the role of soil organisms in regulating C dynamics in prediction of SOC mineralization and retention in the terrestrial ecosystem.


Subject(s)
Ecosystem , Soil , Soil/chemistry , Carbon/analysis , China , Climate
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