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1.
Neuroreport ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38973500

ABSTRACT

Acupuncture can reduce blood pressure, heart rate (HR), and ameliorate cardiac damage by modulating the excitability of the sympathetic nervous system, but the exact mechanism of this effect remains unclear. This study investigated the potential mechanisms of acupuncture in the treatment of cardiac damage in hypertension. Spontaneously hypertensive rats (SHR) were used as the hypertension model with Wistar-Kyoto rats as the control. Manual acupuncture, electroacupuncture, and metoprolol were used as interventions. Systolic and diastolic blood pressure (SBP, DBP) plus HR were monitored with cardiac structure determined using Masson staining. Angiotensin II (Ang II) and norepinephrine in myocardium were detected with ELISA as was Ang(1-7) and gamma aminobutyric acid (GABA) in the rostral ventrolateral medulla (RVLM). Expression of mRNA for collagen type I (Col-I), Col-III, actin α1 (ACTA1), and thrombospondin 4 (THBS4) in myocardium was detected using real-time PCR. Expression of angiotensin converting enzyme (ACE), Ang II, angiotensin II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) proteins in RVLM was monitored using western blot. After manual acupuncture and electroacupuncture treatment, SHRs showed decreased SBP, DBP and HR, reduced myocardial damage. There was decreased expression of the ACE/Ang II/AT1R axis, and increased expression of the ACE2/Ang(1-7)/MasR axis within the RVLM. GABA levels were increased within the RVLM and norepinephrine levels were decreased in myocardial tissue. Metoprolol was more effective than either manual acupuncture or electroacupuncture. Acupuncture directed against hypertensive cardiac damage may be associated with regulation of ACE/Ang II/AT1R and the ACE2/Ang(1-7)/MasR pathway within the RLVM to reduce cardiac sympathetic excitability.

2.
Nat Commun ; 15(1): 3884, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719909

ABSTRACT

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.


Subject(s)
B7-1 Antigen , B7-H1 Antigen , Extracellular Vesicles , Programmed Cell Death 1 Receptor , Extracellular Vesicles/metabolism , Extracellular Vesicles/immunology , Programmed Cell Death 1 Receptor/metabolism , Humans , B7-1 Antigen/metabolism , B7-H1 Antigen/metabolism , B7-H1 Antigen/immunology , Animals , Mice , Cell Line, Tumor , Female , Neoplasms/immunology , Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Immune Tolerance , Mice, Inbred C57BL , Male , Tumor Microenvironment/immunology
3.
Front Immunol ; 15: 1333170, 2024.
Article in English | MEDLINE | ID: mdl-38545112

ABSTRACT

Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.


Subject(s)
Hypertension, Renal , Nephritis , Humans , Inflammation , Cytokines
4.
Environ Sci Pollut Res Int ; 31(18): 26646-26664, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38451456

ABSTRACT

Perfluorinated compounds (PFCs) are persistent organic contaminants that are highly toxic to the environment and bioaccumulate, but their ecotoxic effects on aquatic plants remain unclear. In this study, the submerged plant Vallisneria natans was treated with short-term (7 days) and long-term (21 days) exposures to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) at concentrations of 0, 0.01, 0.1, 1.0, 5.0, and 10 mg/L, respectively. The results showed that both high concentrations of PFOA and PFOS inhibited the growth of V. natans and triggered the increase in photosynthetic pigment content in leaves. The oxidative damage occurred mainly in leaves, but both leaves and roots gradually built up tolerance during the stress process without serious membrane damage. Both leaves and roots replied to short-term stress by activating superoxide dismutase (SOD), catalase (CAT) and polyphenol oxidase (PPO), while peroxidase (POD) was involved under high concentration stress with increasing exposure time. Leaves showed a dose-effect relationship in integrated biomarker response (IBR) values under short-term exposure, and the sensitivity of roots and leaves to PFOS was higher than that of PFOA. Our findings help to increase knowledge of the toxic effects of PFCs and have important reference value for risk assessment and environmental remediation of PFCs in the aquatic ecosystem.


Subject(s)
Alkanesulfonic Acids , Caprylates , Fluorocarbons , Water Pollutants, Chemical , Fluorocarbons/toxicity , Alkanesulfonic Acids/toxicity , Caprylates/toxicity , Water Pollutants, Chemical/toxicity , Hydrocharitaceae/drug effects , Plant Leaves/drug effects
5.
Int Immunopharmacol ; 128: 111545, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38244517

ABSTRACT

Liver ischemia-reperfusion injury (IRI) remains a common issue and with the increasing incidence of Nonalcoholic fatty liver disease (NAFLD), which are more sensitive to IRI, it is crucial to explore the possible strategy to alleviate the steatotic liver IRI. Several modes of cell death are involved in hepatocytes and immune cells during hepatic IRI, and the effects of different cell death inhibitors including apoptosis, necroptosis, pyroptosis, and ferroptosis in steatotic liver IRI have not been investigated. We established 70% IRI model on steatotic liver in mice. Apoptosis, necroptosis, pyroptosis and ferroptosis inhibitors were used to evaluate their effects on liver injury, inflammatory response, and immune cell infiltration. Immunofluorescence and immunohistochemical results demonstrated that there were apoptosis, necroptosis, pyroptosis, and ferroptosis in the progression of IRI in steatotic liver. All four types of cell death inhibitors showed protective effects, but ferroptosis inhibitor Fer-1 and pyroptosis inhibitor VX765 exerted better protective effects compared the apoptosis inhibitor Z-VAD and necroptosis inhibitor Nec-1. Further, we found that pyroptosis occurred mainly in macrophages and ferroptosis occured primarily in hepatocytes during steatotic liver IRI. Ferroptosis in heaptocytes and pyroptosis in macrophages are two major cell death types involved in steatotic liver IRI and inhibiting these cell death exerted good protective effects.


Subject(s)
Non-alcoholic Fatty Liver Disease , Reperfusion Injury , Animals , Mice , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Hepatocytes/metabolism , Apoptosis , Reperfusion Injury/metabolism
6.
Int Orthop ; 47(11): 2843-2850, 2023 11.
Article in English | MEDLINE | ID: mdl-37632529

ABSTRACT

PURPOSE: This study aims to evaluate the efficacy and safety of the full-endoscopic lumbar discectomy (FELD) via lateral superior articular process (LSAP) approach and full-endoscopic transforaminal discectomy (FETD) for treating far lateral lumbar disk herniation (FFLDH). METHODS: From January 2020 to June 2022, patients who were diagnosed as FLLDH underwent the FELD via LSAP approach or FETD. The operation time, estimated blood loss, length of hospital stays, and complications were recorded. The visual analog scale (VAS) for back pain, VAS for leg pain, and the Oswestry Disability Index (ODI) scores was measured during preoperative and postoperative follow-up. RESULTS: Thirty-two patients were enrolled in this study, of which 12 patients were treated with the FELD via LSAP approach (LSAP-FELD group) and 20 patients underwent FETD (FETD group). The LSAP-FELD group exhibited significantly shorter operation times and hospital stays compared to the FETD group, while no statistically significant differences were observed in intraoperative blood loss and complication rates. There were no significant differences in the VAS for back pain, the VAS for leg pain, and the ODI score between the two groups preoperatively and three days, three months, and the last follow-up postoperatively. CONCLUSIONS: Both the FELD via LSAP approach and FETD have demonstrated favourable clinical efficacy in the treatment of FLLDH. Notably, the FELD via LSAP approach shows the advantages of shorter operation time and hospital stays.


Subject(s)
Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Intervertebral Disc Displacement/etiology , Retrospective Studies , Lumbar Vertebrae/surgery , Diskectomy/adverse effects , Endoscopy/adverse effects , Back Pain/etiology , Treatment Outcome
7.
Front Neurosci ; 17: 1203915, 2023.
Article in English | MEDLINE | ID: mdl-37539383

ABSTRACT

Autoimmune encephalitis, a class of encephalitis, is clinically characterized by multifocal or diffuse brain injury, including aberrant mental behavior, convulsions, and near-event memory impairment. In this article, we describe a female patient with autoimmune encephalitis who tested positive for leucine-rich glioma inactivated 1 (LGI1) antibodies and had hippocampal inflammatory edema in the lesion area. During the first 3 months of her illness, the patient primarily experienced memory loss, the onset of rigid twitching in her extremities that lasted for 1 min while in remission, and incontinence. After gamma globulin administration, methylprednisolone shock, and other symptomatic therapies during hospitalization, the patient's psychiatric symptoms and seizures improved considerably; however, she did not fully recover her memory. After receiving fire acupuncture for 6 months, the patient's understanding, orientation, and calculation skills improved considerably. Her memory and mental state were also improved at the follow-up visit. In this case, the use of fire acupuncture for the treatment of autoimmune encephalitis resulted in favorable outcomes with important benefits for conditions affecting the central nervous system; however, more convincing data are required to support the effectiveness of this treatment method.

8.
World Neurosurg ; 179: e348-e358, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37634669

ABSTRACT

BACKGROUND: Accurately predicting the risk of lower extremity (LE) radiating pain after surgery is an important endeavor for spinal surgeons. Our study aimed to identify risk factors for LE radiating pain after decompression with full-endoscopic lumbar discectomy (FELD) and develop a nomogram. METHODS: We retrospectively reviewed the medical data of patients with lumbar disc herniation who underwent FELD. Two hundred thirty-five patients diagnosed at our hospital from January 2015 to December 2020 were used for model development. The independent risk factors for LE radiating pain after surgery were determined by least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis. A nomogram was developed to predict the risk of LE radiating pain based on independent risk factors. Receiver operating characteristic curve, calibration curve, and decision curve analyses were used to evaluate the predictive performance. The nomogram was further verified by an independent cohort. RESULTS: Three hundred seventy-five patients were enrolled in this study, with 102 patients in the training cohort reporting LE radiating pain after FELD, while 133 patients did not. In the validation cohort, 57 patients reported LE radiating pain after FELD, while 83 patients did not. The model was established by multivariate logistic regression analysis. The risk factors included a higher Michigan State University classification of herniated discs, increased disease course, increased time of surgery, reduced lateral recess width, and an interlaminar surgical approach, compared to transforaminal approach. The C-indices and the area under the receiver operating characteristic curve of the predictive model demonstrated good discrimination. Good predictive performance and accuracy were also observed in the validation cohort. CONCLUSIONS: A novel nomogram for predicting recurrent LE radiating pain within 1 week after FELD was established and validated. More aggressive pain management strategies should be considered for patients at high risk of LE radiating pain after surgery, as predicted by this model.


Subject(s)
Intervertebral Disc Displacement , Nomograms , Humans , Retrospective Studies , Diskectomy/adverse effects , Intervertebral Disc Displacement/complications , Pain/etiology , Lower Extremity/surgery , Lumbar Vertebrae/surgery
9.
Front Neurosci ; 17: 1161578, 2023.
Article in English | MEDLINE | ID: mdl-37304030

ABSTRACT

Aim: To observe the effects of acupuncture manipulations on blood pressure and brain function in spontaneously hypertensive rats and elucidate the anti-hypertensive effect of the manipulations' central mechanism. Methods: This study used acupuncture twirling reinforcing, acupuncture twirling reducing, and acupuncture twirling uniform reinforcing-reducing manipulations to act on the bilateral TaiChong point of rats. The depth of acupuncture was 1.5-2 mm, and twisting was performed at a frequency of 60 times/min within ±360° for 3 min, followed by the needle being retained for 17 min. Functional magnetic resonance imaging was performed at the end of the intervention. Regional homogeneity and amplitude of low-frequency fluctuations were used to assess the differences in brain regions in each group of rats, and the core brain region (left hypothalamus) among the differential brain regions was selected as the seed for functional connectivity analysis. Results: (1) The anti-hypertensive effect was achieved by acupuncture manipulations, and the anti-hypertensive effect of twirling reducing manipulation on spontaneously hypertensive rats was better than that of twirling uniform reinforcing-reducing and twirling reinforcing manipulations. (2) After regional homogeneity and amplitude of low-frequency fluctuations analyses, the hypothalamus, the brain region related to blood pressure, was activated in the twirling uniform reinforcing-reducing manipulation group; the corpus callosum and cerebellum were activated in the twirling reinforcing manipulation group; and the hypothalamus, olfactory bulb, corpus callosum, brainstem, globus pallidum, and striatum were activated in the twirling reducing manipulation group. (3) According to the functional connectivity analysis, different acupuncture manipulations increased the functional connections between seed points and the brainstem, olfactory bulb, and cerebellum, etc. Conclusion: These results suggest that acupuncture manipulations achieved the hypotensive effect and the twirling reducing manipulation had a better hypotensive effect on spontaneously hypertensive rats than twirling uniform reinforcing-reducing and twirling reinforcing manipulations; the central mechanism of the anti-hypertensive effect of twirling reinforcing and reducing manipulation may be related to the activation of brain regions associated with blood pressure regulation and the functional connections between them. Furthermore, brain regions involved in motor control, cognition, and hearing were also activated. We hypothesize that activation of these brain regions may help prevent or mitigate the onset and progression of hypertensive brain damage.

10.
Zhongguo Zhong Yao Za Zhi ; 48(6): 1620-1631, 2023 Mar.
Article in Chinese | MEDLINE | ID: mdl-37005850

ABSTRACT

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.


Subject(s)
Alzheimer Disease , Drugs, Chinese Herbal , Animals , Mice , Rats , Proto-Oncogene Proteins c-akt , Network Pharmacology , Alzheimer Disease/drug therapy , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/genetics , Tandem Mass Spectrometry , Drugs, Chinese Herbal/pharmacology
11.
Front Neurosci ; 17: 1129688, 2023.
Article in English | MEDLINE | ID: mdl-36968479

ABSTRACT

Introduction: Chronic hypertension may have a contributory role toward cognitive impairment. Acupuncture exerts protective effects on cognitive functions while controlling the blood pressure. However, the neural mechanism underlying the dual attenuating effect of acupuncture remains unclear. In this study, we investigated the effects of electroacupuncture (EA) and manual acupuncture (MA) on the functional activity of the brain regions of spontaneously hypertensive rats (SHRs) by through resting-state functional magnetic resonance imaging (rs-fMRI). We also evaluated the differences in these functional activities between the EA and MA groups. Methods: We randomly assigned 30 SHRs into the EA, MA, and model (SHR) groups. Wistar Kyoto rats (n = 10) were used as normal control (WKY). The interventions were administered once every alternate day for 12 weeks. The systolic blood pressure of all rats was recorded every 2 weeks until the end of the intervention. After the intervention, rs-fMRI scanning was performed to access the whole brain data of rats randomly selected from each group evenly. The amplitude of low frequency fluctuation (ALFF) analysis, regional homogeneity (ReHo) analysis, and functional connectivity (FC) analysis were also conducted. The Morris water maze (MWM) test was conducted to evaluate the learning and memory of the rats. Hematoxylin-eosin staining and Nissl staining were performed to observe histopathological changes in the key brain regions. Results: We demonstrated that, when compared with the SHR group, the EA and MA groups had significantly lower blood pressure and better performance for behavioral test indices, and that the effect of EA was better than that of MA. ALFF and ReHo analyses revealed enhancement of the neuronal activity of some functionally impaired brain areas in the EA and MA groups. The main callback brain regions included the hypothalamus, entorhinal cortex, brain stem, prelimbic cortex, cingulate cortex, corpus callosum, and cerebellum. The FC analysis demonstrated that EA and MA enhanced the functional connectivity between the seeds and brain regions such as the brain stem, entorhinal cortex, hippocampus, prelimbic cortex, and cerebellum. The pathological test of the entorhinal cortex also verified the protective effect of acupuncture on the neuronal functional activity. Discussion: Our findings suggested that EA and MA exhibited attenuating effects on hypertension and cognitive dysfunction by enhancing the functional activities in the corresponding brain regions. Moreover, EA activated more callback brain regions and functional connectivity than MA, which may explain why the effect of EA was better than that of MA.

12.
Phytochemistry ; 209: 113613, 2023 May.
Article in English | MEDLINE | ID: mdl-36804478

ABSTRACT

Three unprecedented thioether-linked dimeric pyrimidines, namely ligusticumines A-C, together with twelve known compounds were isolated and identified from the traditional Chinese medicinal-edible herb, Ligusticum striatum DC. The structures of all the isolated compounds were determined from NMR, HRESIMS and X-ray diffraction spectroscopies. Additionally, a novel 3-step synthetic route was developed to synthesize ligusticumine C by substitution, thiolation and coupling, with an overall yield of 5.4%. The inhibitory activities of the isolated compounds against phosphatidylinositol 3-kinase (PI3K) were tested, of which, (3S)-butylphthalide, a characteristic component of L. striatum, showed a potent inhibitory effect on PI3Kα (IC50: 3.6 µg/mL).


Subject(s)
Ligusticum , Plants, Medicinal , Ligusticum/chemistry , Phosphatidylinositol 3-Kinases , Pyrimidines/chemistry , Pyrimidines/pharmacology , Magnetic Resonance Spectroscopy
13.
Am J Transplant ; 23(3): 336-352, 2023 03.
Article in English | MEDLINE | ID: mdl-36695693

ABSTRACT

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.


Subject(s)
Liver Transplantation , MicroRNAs , Animals , Humans , Rats , Leukocytes, Mononuclear/metabolism , Macrophages/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Procollagen/metabolism , Procollagen/pharmacology
14.
Int Orthop ; 47(3): 819-830, 2023 03.
Article in English | MEDLINE | ID: mdl-36542140

ABSTRACT

PURPOSE: Current findings suggest that minimally percutaneous endoscopic lumbar discectomy (PELD) is a practical therapeutic approach for lumbar disc herniation (LDH). However, some patients still end up with residual low back pain, even after surgery. Our study aims to construct and validate a nomogram to predict residual low back pain after PELD. METHODS: The medical records of 355 LDH patients admitted to the author's hospital were retrospectively analyzed between January 2019 and December 2021. The patients were randomly divided into two groups with a ratio of 7:3, namely a modelling group and a validation group. The univariable logistics and multivariable regression methods were used to screen the independent risk factors. A nomogram was then drawn using independent risk factors selected from the univariable and multivariable regression analyses. The concordance index (C-index), the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis were used to evaluate the nomogram's performance. Finally, the accuracy of the nomogram was verified by a validation cohort. RESULTS: 36.6% (130/355) of patients showed low back pain after percutaneous endoscopic lumbar discectomy, while 63.4% (225/355) showed no symptoms. Multivariable logistical regression analysis showed that Modic change (p < 0.05, OR = 1.813), fatty infiltration of the paravertebral muscle (p < 0.05, OR = 2.935), and edema of lumbodorsal fascia (p = 0.049, OR = 1.611) were significant risk factors for post-operative residual back pain. Moreover, the C-index of the predictive nomogram was 0.743 (0.681-0.805), the area under the receiver operating characteristic curve (AUC) value was 0.739, and the DCA results exhibit a net benefit between 0.16 and 0.66. The above internal validation methods demonstrate the nomogram's good predictive capability. CONCLUSION: Each variable in the model had a quantitatively corresponding risk score, which can be used in predicting residual low back pain after PELD.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Low Back Pain , Humans , Intervertebral Disc Displacement/surgery , Intervertebral Disc Displacement/etiology , Low Back Pain/epidemiology , Low Back Pain/etiology , Low Back Pain/surgery , Diskectomy, Percutaneous/adverse effects , Diskectomy, Percutaneous/methods , Retrospective Studies , Nomograms , Treatment Outcome , Lumbar Vertebrae/surgery , Endoscopy/adverse effects , Endoscopy/methods
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970634

ABSTRACT

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.


Subject(s)
Animals , Mice , Rats , Proto-Oncogene Proteins c-akt , Network Pharmacology , Alzheimer Disease/drug therapy , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/genetics , Tandem Mass Spectrometry , Drugs, Chinese Herbal/pharmacology
16.
Neurol India ; 70(Supplement): S230-S238, 2022.
Article in English | MEDLINE | ID: mdl-36412374

ABSTRACT

Background: The standard recommended and common reconstruction method for spinal tuberculosis is titanium mesh bone graft and autogenous iliac crest. However, these methods have their own disadvantages. Objective: To evaluate the clinical efficacy of one-stage posterior debridement with iliac bone graft, titanium mesh bone graft, or nanohydroxyapatite/polyamide-66 cage in thoracic and lumbar tuberculosis. Materials and Methods: Between January 2013 and December 2018, 57 patients with thoracic or lumbar tuberculosis were treated by interbody bone graft combined with posterior internal fixation after debridement. Thirteen patients were treated with iliac bone graft to construct the stability of the vertebral body, 26 patients were treated with titanium mesh bone graft, and 18 patients were treated with nanohydroxyapatite/polyamide-66 cage bone graft. The main clinical results were evaluated by intervertebral height, cage subsidence, operation time, operative blood loss, postoperative hospitalization, postoperative complications, visual analog scale (VAS) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, and bone graft fusion time. All the outcomes were recorded and analyzed by statistical methods. Results: The mean follow-up time was 24.5 months. Neurologic function was improved in most patients at the last follow-up. There were significant differences in ESR, CRP, and VAS score between preoperative and postoperative values; however, there were no significant differences in ESR, CRP, and VAS score among the three groups. There were no significant differences in operation time, blood loss, postoperative hospitalization, and postoperative complications among the three groups at discharge. There was no significant difference in ASIA grade among the three groups at the last follow-up. Nanohydroxyapatite/polyamide-66 cage group had a lower cage subsidence (P = 0.013). The bone graft fusion time of the nanohydroxyapatite/polyamide-66 cage group was significantly shorter than the iliac bone graft group and the titanium mesh bone graft (P < 0.05). Conclusions: The follow-up outcomes showed that the method involving one-stage posterior debridement and internal fixation, interbody graft, and fusion is an effective and safe surgical method for patients with thoracic and lumbar tuberculosis. The incidence rate of cage subsidence was less and the bone graft fusion time was shorter with nanohydroxyap atite/polyamide 66 cage when compared with iliac bone graft and titanium mesh bone graft in the surgical treatment of thoracic and lumbar tuberculosis. Nanohydroxyapatite/polyamide-66 cage has a promising application prospect to be a new bone graft material.


Subject(s)
Spinal Fusion , Tuberculosis, Spinal , Humans , Ilium/surgery , Titanium , Nylons , Thoracic Vertebrae/surgery , Surgical Mesh/adverse effects , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Tuberculosis, Spinal/surgery , Postoperative Complications/etiology , Postoperative Hemorrhage/etiology
17.
Drug Des Devel Ther ; 16: 4061-4076, 2022.
Article in English | MEDLINE | ID: mdl-36448035

ABSTRACT

Background: Triptolide, a major active ingredient isolated from Tripterygium wilfordii Hook f., is effective in the treatment of membranous nephropathy (MN); however, its pharmacological mechanism of action has not yet been clarified. We applied an approach that integrated network pharmacology and experimental validation to systemically reveal the molecular mechanism of triptolide in the treatment of MN. Methods: First, potential targets of triptolide and the MN-related targets were collected from publicly available database. Then, based on a protein-protein interaction network as well as GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to unravel therapeutic targets and pathways. Moreover, molecular docking was applied to validate the interactions between the triptolide and hub targets. Finally, we induced passive Heymann nephritis (PHN) rat models and validated the possible molecular mechanisms of triptolide against MN. Results: The network pharmacology results showed that 118 intersected targets were identified for triptolide against MN, including mTOR, STAT3, CASP3, EGFR and AKT1. Based on enrichment analysis, signaling pathways such as PI3K/AKT, MAKP, Ras and Rap1 were involved in triptolide treatment of MN. Furthermore, molecular docking confirmed that triptolide could bind with high affinity to the PIK3R1, AKT1 and mTOR, respectively. Then, in vivo experiments indicated that triptolide can reduce 24 h urine protein (P < 0.01) and protect against renal damage in PHN. Serum albumin level was significantly increased and total cholesterol, triglycerides, and low-density lipoprotein levels were decreased by triptolide (P < 0.05). Compared with PHN group, triptolide treatment regulated the PI3K/AKT/mTOR pathway according to Western blot analyses. Conclusion: Triptolide could exert antiproteinuric and renoprotective effects in PHN. The therapeutic mechanism of triptolide may be associated with the regulation of PI3K/AKT/mTOR signaling pathway. This study demonstrates the pharmacological mechanism of triptolide in the treatment of MN and provides scientific evidence for basic and clinical research.


Subject(s)
Glomerulonephritis, Membranous , Animals , Rats , Glomerulonephritis, Membranous/drug therapy , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine Kinases
18.
Development ; 149(17)2022 09 01.
Article in English | MEDLINE | ID: mdl-36052695

ABSTRACT

Stomata are epidermal pores that control gas exchange between plants and the atmosphere. In Arabidopsis, the ERECTA family (ERECTAf) receptors, including ERECTA, ERECTA-LIKE 1 (ERL1) and ERL2, redundantly play pivotal roles in enforcing the 'one-cell-spacing' rule. Accumulating evidence has demonstrated that the functional specificities of receptors are likely associated with their differential subcellular dynamics. The endoplasmic reticulum (ER)-resident chaperone complex SDF2-ERdj3B-BiP functions in many aspects of plant development. We employed pharmacological treatments combined with cell biological and biochemical approaches to demonstrate that the abundance of ERECTA was reduced in the erdj3b-1 mutant, but the localization and dynamics of ERECTA were not noticeably affected. By contrast, the erdj3b mutation caused the retention of ERL1/ERL2 in the ER. Furthermore, we found that the function of SDF2-ERdj3B-BiP is implicated with the distinct roles of ERECTAf receptors. Our findings establish that the ERECTAf receptor-mediated signaling in stomatal development is ensured by the activities of the ER quality control system, which preferentially maintains the protein abundance of ERECTA and proper subcellular dynamics of ERL1/ERL2, prior to the receptors reaching their destination - the plasma membrane - to execute their functions.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Carrier Proteins/metabolism , Endoplasmic Reticulum/metabolism , Gene Expression Regulation, Plant , HSP40 Heat-Shock Proteins/genetics , HSP40 Heat-Shock Proteins/metabolism , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Protein Serine-Threonine Kinases , Receptors, Cell Surface/genetics
19.
Front Surg ; 9: 916087, 2022.
Article in English | MEDLINE | ID: mdl-35784932

ABSTRACT

Objective: This study aimed to compare postoperative outcomes in surgical and patient-reported outcomes (PROs) between percutaneous endoscopic lumbar interbody fusion (PE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar spinal stenosis (LSS). Methods: We reviewed a total of 89 patients undergoing single-level surgery for lumbar spinal stenosis from January 2018 to July 2021. The cases were categorized as PE-LIF (Group PE-LIF, 41 cases) or MIS-TLIF (Group MIS-TLIF, 48 cases) approach. Parameters obtained at baseline through at least six months of follow-up were collected. The surgical outcomes involving the operative time, estimated blood loss, postoperative bed staying time, and length of hospital stays were analyzed. PROs included the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), modified MacNab standard evaluation, intervertebral fusion rate, and postoperative complications. Results: A total of 89 patients were included in this analysis involving 41 patients who underwent PE-LIF and 48 patients who underwent MIS-TLIF. The 2 groups were similar in gender, age, body mass index, follow-up time and surgery levels (P > 0.05), and were not significantly different in the length of hospital stays (P > 0.05). PE-LIF had a significantly longer operative time, greater fluoroscopy time, lower estimated blood loss and shorter bed rest time than MIS-TLIF. Both groups improved significantly from baseline for the VAS and ODI scores. PE-LIF was associated with a lower VAS score for back pain at three-day after surgery. There were no significant differences between PE-LIF and MIS-TLIF in the excellent or good rates and intervertebral fusion rates at the last follow-up (P > 0.05). As for related complications, there were no significant complications occurred, and no significant differences were seen in the complications between both groups (P > 0.05). Conclusions: To summarize, PE-LIF and MIS-TLIF are both safe and effective for LSS. PE-LIF has a definite short-term curative effect with less trauma.

20.
Plant Cell ; 34(10): 3665-3684, 2022 09 27.
Article in English | MEDLINE | ID: mdl-35897146

ABSTRACT

The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)-ERdj3B-binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2-ERdj3B-BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2-ERdj3B-BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2-ERdj3B-BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Carrier Proteins/metabolism , HSP40 Heat-Shock Proteins/metabolism , Heat-Shock Response , Ovule/metabolism , Protein Serine-Threonine Kinases
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