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1.
Toxicol Lett ; 397: 11-22, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723914

ABSTRACT

Matrine (MT) has shown promising efficacy in various cancers and chronic hepatitis; however, its clinical application is limited because of its side effects. Our previous studies have indicated that MT can induce severe hepatotoxicity and nephrotoxicity. The current study aimed to investigate its cardiotoxicity and potential underlying mechanisms in H9c2 cells. Our results showed that MT induced H9c2 cell death and disrupted the cellular membrane integrity. Moreover, MT decreased glutathione (GSH) and cysteine (Cys) levels, and increased Fe2+, lipid peroxidation, reactive oxygen species (ROS), and MDA levels, ultimately leading to ferroptosis. Interestingly, these phenomena were alleviated by the ferroptosis inhibitor Fer-1, whereas MT-induced ferroptosis was exacerbated by the ferroptosis agonist RSL3. In addition, MT significantly reduced FTH, Nrf2, xCT, GPX4, and FSP1 protein levels and inhibited the transcriptional activity of Nrf2 while increasing TFR1 protein levels. Supplementation with Nrf2 agonist (Dimethyl fumarate, DMF) or selenium (Sodium selenite, SS) and CoQ10 alleviated MT-induced cytotoxic effects in H9c2 cells. These results suggest that ferroptosis, which is mediated by an imbalance in the Nrf2 antioxidant system, is involved in MT-induced cardiac toxicity.

2.
Pak J Pharm Sci ; 37(2): 385-397, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767106

ABSTRACT

A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the Tmax of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the Cmax was reduced from 6.162µg/mL to 3.244µg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC0-24 of 19.578 µg•h•mL-1) compared with the commercial drug (AUC0-24 of 17.388 µg•h•mL-1) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.


Subject(s)
Delayed-Action Preparations , Pantoprazole , Suspensions , Pantoprazole/pharmacokinetics , Pantoprazole/administration & dosage , Animals , Male , Rats , Drug Liberation , Biological Availability , Administration, Oral , Drug Compounding , Excipients/chemistry , Rats, Sprague-Dawley
3.
Nanotechnology ; 35(29)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38593759

ABSTRACT

Herein, we employ molecular dynamics simulations to decode the friction properties and phonon energy dissipation between black phosphorus layers. The observations reveal the influence of three factors, temperature, velocity, and normal load, on the friction force of monolayer/bilayer black phosphorus. Specifically, friction is negatively correlated with layer thickness and temperature, and positively correlated with velocity and normal load. The change in friction force is further explained in terms of frictional energy dissipation, and supplemented by the height of potential barriers as well as the number of excited phonons. From the phonon spectrum analysis, the phonon number at the contact interface is found to be higher than that at the non-contact interface. This is due to the larger distance of the contact interface atoms deviate from their equilibrium positions, resulting in higher total energy generated by more intense oscillations, and therefore contributes greater to friction.

4.
Biomed Pharmacother ; 174: 116542, 2024 May.
Article in English | MEDLINE | ID: mdl-38574620

ABSTRACT

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI.


Subject(s)
14-3-3 Proteins , Apoptosis , Autophagy , Catechin , Catechin/analogs & derivatives , Ferroptosis , Myocardial Reperfusion Injury , Catechin/pharmacology , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/drug therapy , Animals , Autophagy/drug effects , Apoptosis/drug effects , Ferroptosis/drug effects , 14-3-3 Proteins/metabolism , Male , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Reactive Oxygen Species/metabolism , Mice , Cardiotonic Agents/pharmacology , Cell Survival/drug effects , Rats, Sprague-Dawley
5.
ACS Appl Mater Interfaces ; 16(19): 25519-25528, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38593204

ABSTRACT

This work investigates the coupling effect of structural lubrication and thermal excitation on phononic friction between black phosphorus (BP) layers. As the rotation angle increases from commensurate to incommensurate states, the friction gradually decreases at any temperature. However, the role of temperature in friction depends on commensurability. For a rotation angle less than 10°, increasing temperature leads to a decrease in friction due to thermal excitation. Conversely, when the rotation angle exceeds 10°, elevated temperature results in an increase in friction due to the effect of thermal collision. At a critical rotation angle of 10°, higher temperatures lead to reduced friction through thermal lubrication at low speeds, and at large speeds, the thermal excitation duration becomes so short that the role of thermal lubrication is weakened, and instead thermal collision dominates. Further research reveals that BP's ability to withstand different maximum speeds is also determined by commensurability. Finally, a method to measure the sliding period length of a rotated tip through an unrotated substrate potential energy topography is proposed and simply verified by using the phonon spectrum.

6.
Drug Des Devel Ther ; 18: 1247-1262, 2024.
Article in English | MEDLINE | ID: mdl-38645988

ABSTRACT

Purpose: Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN. Methods: The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid-Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting. Results: SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells. Conclusion: SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.


Subject(s)
Apoptosis , B-Lymphocytes , Cell Proliferation , Glomerulonephritis, IGA , Morphinans , T-Lymphocytes , Morphinans/pharmacology , Morphinans/chemistry , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/pathology , Animals , Apoptosis/drug effects , Rats , Cell Proliferation/drug effects , B-Lymphocytes/drug effects , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Male , Dose-Response Relationship, Drug , Disease Models, Animal , Rats, Sprague-Dawley , Structure-Activity Relationship , Protective Agents/pharmacology , Protective Agents/chemistry , Humans , Cells, Cultured
7.
BMC Gastroenterol ; 24(1): 111, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38491346

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new term for diagnosing fatty liver disease, which is considered to be a multi-systemic disease with multiple extrahepatic manifestations, including sarcopenia. The link between sarcopenia and MAFLD remains uncertain, especially among young and middle-aged adults. Thus, we examined the relationship between MAFLD and sarcopenia in young and middle-aged individuals in this study. METHODS: A total of 2214 individuals with laboratory tests, dual-energy X-ray absorptiometry and ultrasound transient elastography from NHANES 2017-2018 were selected for this study. MAFLD was diagnosed as fatty liver disease with any one of the situations: overweight/obesity, diabetes mellitus, presence of metabolic dysregulation. Sarcopenia was defined by appendicular lean mass adjusted for body mass index (BMI). Multivariable logistic regression and restricted cubic spline (RCS) model were applied to explore the relationship between MAFLD and sarcopenia, and the mediation analyses were also conducted. Moreover, subgroup analyses stratified by BMI and lifestyles were done. RESULTS: The prevalence of MAFLD was 47.85%, and nearly 8.05% of participants had sarcopenia. The prevalence of sarcopenia was higher in participants with MAFLD (12.75%; 95% CI 10.18-15.31%) than in the non-MAFLD (3.73%; 95% CI 2.16-5.31%). MAFLD was significantly positively associated with sarcopenia after adjustments [OR = 2.87 (95% CI: 1.62-5.09)]. Moreover, significant positive associations were observed between liver fibrosis and sarcopenia prevalence in MAFLD patients (OR = 2.16; 95% CI 1.13-4.15). The RCS curve revealed that MAFLD was linearly associated with sarcopenia. The relationship between the MAFLD and sarcopenia were mediated by C-reactive protein (mediation proportion: 15.9%) and high-density lipoprotein cholesterol (mediation proportion: 18.9%). Subgroup analyses confirmed the association between MAFLD and sarcopenia differed in different lifestyle groups. CONCLUSIONS: Both MAFLD prevalence and severity was significantly associated with sarcopenia. Thus, clinicians should advise comorbidity screening and lifestyle changes to young and middle-aged patients.


Subject(s)
Non-alcoholic Fatty Liver Disease , Sarcopenia , Adult , Middle Aged , Humans , Nutrition Surveys , Sarcopenia/complications , Sarcopenia/epidemiology , Body Mass Index , C-Reactive Protein , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology
8.
BMC Med ; 21(1): 414, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37907866

ABSTRACT

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Prenatal Exposure Delayed Effects , Starvation , Adult , Humans , Middle Aged , China , Cohort Studies , Diabetes Mellitus, Type 2/complications , East Asian People , Famine , Microbiota , Starvation/complications , Adolescent , Young Adult , Aged , Aged, 80 and over
9.
Chem Biodivers ; 20(9): e202301017, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37603393

ABSTRACT

Nine new compounds, including streptothiomycin A-E (1-5), two cyclopentenones (6, 7), one α-pyrone (8), wailupemycin Q (20), along with sixteen known compounds were identified from a rhizosphere strain Streptomyces sp. DS-27 derived from the marine cordgrass Spartina alterniflora under two different culture conditions. All of the structures were elucidated by extensive analysis of 1D/2D NMR and HR-ESI-MS data. The absolute configurations were determined by NOESY analysis, ECD, specific rotation and GIAO NMR calculations, and DP4+ probability analysis. Bioactivity investigation showed that compounds 5 and 7 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.


Subject(s)
Antineoplastic Agents , Streptomyces , Antineoplastic Agents/pharmacology , Streptomyces/chemistry , Magnetic Resonance Spectroscopy , Pyrones/chemistry , Molecular Structure
10.
Polymers (Basel) ; 15(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37631492

ABSTRACT

Using fiber and cement to modify waste slurry and apply it to roads is an effective way to recycle waste slurry. A new type of road material, fiber-cement-modified waste slurry (FRCS), was prepared in this study. The static and dynamic characteristics of the cement soil were studied using an unconfined compressive strength test and dynamic triaxial test. The results show that the optimum fiber content of FRCS is 0.75%. In the unconfined compressive strength test, under this fiber content, the unconfined compressive strength (UCS) of the FRCS is the largest, and the elastic modulus and modulus strength ratio are both the smallest, indicating that the tensile properties of the cement slurry have been enhanced. In the dynamic triaxial test, the hysteretic curve of the FRCS tends to be stable with the increase in the number of cycles, the dynamic elastic modulus of the FRCS decreases first and then increases with the increase in the dosage, while the damping ratio becomes stable after a rapid decline, and the fiber incorporation increases the cumulative strain of the soil-cement under low-stress cycles, indicating that the ductility of the FRCS is improved. In addition, a cumulative strain prediction model of the FRCS is established in this paper, which can provide a reference for the resource application of waste slurry in road engineering.

11.
Heliyon ; 9(8): e18968, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37636455

ABSTRACT

Hypercalcaemia associated with malignancy is a complication of advanced tumors. Lactic acidosis is also an extremely rare paraneoplastic syndrome of malignancy, and the presence of both usually indicates an extremely poor prognosis for the tumour. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma and is also a common aggressive lymphoma. It is extremely rare for patients with diffuse large B-cell lymphoma to develop both hypercalcaemia and severe lactic acidosis. In this article, we report a case of CD5 positive diffuse large B-cell lymphoma with hypercalcaemic crisis and persistent lactic acidosis, in which calcium was rapidly reduced to normal after rehydration, diuresis, calcitonin and zoledronate, and continuous renal replacement therapy (CRRT). After correction of acidosis with sodium bicarbonate, diuresis, vitamin B1 and CRRT, the patient's lactate remained at a high level. The aim of this article is to analyse the experience of the combination of hypercalcaemia and intractable lactic acidosis, which should be considered as a serious electrolyte disorder possibly associated with abnormal metabolism of malignant tumors, and to identify and treat the primary lesion as early as possible.

12.
Blood Cancer J ; 13(1): 124, 2023 08 18.
Article in English | MEDLINE | ID: mdl-37591873

ABSTRACT

T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated with distinct tumor microenvironments and patient outcome. We identified four immune subgroups with differing T-cell phenotypes and the prevalence of certain T-cell subsets was associated with patient survival. Patients with increased T cells with early differentiation stage tended to have a significantly better survival than patients with increased T-cells of late differentiation stage. Specifically, CD57+ TFH cells, with a late-stage differentiation phenotype, were significantly more abundant in FL patients who had early disease progression and therefore correlated with an inferior survival. Single cell analysis (CITE-seq) revealed that CD57+ TFH cells exhibited a substantially different transcriptome from CD57- TFH cells with upregulation of inflammatory pathways, evidence of immune exhaustion and susceptibility to apoptosis. Taken together, our results show that different tumor microenvironments among FL patients are associated with variable T-cell phenotypes and an increased prevalence of CD57+ TFH cells is associated with poor patient survival.


Subject(s)
Lymphoma, Follicular , T Follicular Helper Cells , Humans , Tumor Microenvironment , Cell Differentiation , Phenotype
13.
Dev Cell ; 58(21): 2376-2392.e6, 2023 11 06.
Article in English | MEDLINE | ID: mdl-37643613

ABSTRACT

Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.


Subject(s)
Embryo Implantation , Epithelial Cells , Pregnancy , Female , Humans , Animals , Mice , Embryo Implantation/genetics , Embryonic Development , Endometrium/physiology , Cell Differentiation
14.
Quant Imaging Med Surg ; 13(7): 4405-4414, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37456300

ABSTRACT

Background: Although shear wave elastography (SWE) has been found to have the potential to evaluate skin lesions in systemic sclerosis (SSc), current research fails to answer the following questions: (I) can high-frequency ultrasound (HFUS) and SWE at multiple sites throughout the body distinguish SSc subtypes; (II) is HFUS and SWE at every site equally affected by clinical characteristics; and (III) is SWE a supplement or a choice to HFUS. This prospective study aimed to compare the value of SWE-based skin stiffness and HFUS-based skin thickness in distinguishing different SSc subtypes, verify the influence of clinical features on SWE and HFUS, and provide a basis for the screening of the optimal evaluation sites and indicators in the future. Methods: Forty-nine limited and 51 diffuse SSc patients were included in this study. Their skin was assessed at 17 sites by palpation using the modified Rodnan skin score (mRSS), skin thickness measured by HFUS, and skin stiffness by SWE. Clinical features, including age, sex, body mass index, and disease duration, were collected. Results: The diffuse SSc patients had higher skin stiffness at most sites (P<0.05), except for the finger, foot, and forehead, and a thicker skin layer at most sites (P<0.05), except for the finger. The area under the curve (AUC) of HFUS, SWE, and the combination of the two in distinguishing diffused and limited SSc were 0.866, 0.921, and 0.973, respectively. The differences were statistically significant (combination vs. SWE, P=0.002, combination vs. HFUS, P=0.021). Longer disease duration was associated with a thinner skin layer at the forearm, arm, chest wall, abdominal wall, and thigh in limited SSc, including the leg in diffused SSc. SWE was less affected by clinical features than HFUS. SWE could achieve greater discrimination between different mRSSs at multiple sites, such as fingers and arms, than HFUS. Conclusion: For the assessment of SSc skin, SWE has several advantages over HFUS, including less influence by clinical features and greater sensitivity to discriminate different mRSSs. SWE has the potential to become a primary imaging assessment tool as well as HFUS.

15.
Chemosphere ; 337: 139445, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37423410

ABSTRACT

The effects of microbial electrolysis cells (MECs) at three applied voltages (0.8, 1.3, and 1.6 V) on simultaneously enhancing methanization and reducing hydrogen sulfide (H2S) production in the anaerobic digestion (AD) of sewage sludge were studied. The results showed that the MECs at 1.3 V and 1.6 V simultaneously enhanced the methane production by 57.02 and 12.70% and organic matter removal by 38.77 and 11.13%, and reduced H2S production by 94.8 and 98.2%, respectively. MECs at 1.3 V and 1.6 V created a micro-aerobic conditions for the digesters with oxidation-reduction potential as -178∼-232 mv, which enhanced methanization and reduced H2S production. Sulfur reduction, H2S and elemental sulfur oxidation occurred simultaneously in the ADs at 1.3 V and 1.6 V. The relative abundances of sulfur-oxidizing bacteria increased from 0.11% to 0.42% and those of sulfur-reducing bacteria decreased from 1.24% to 0.33% when the applied voltage of MEC increased from 0 V to 1.6 V. Hydrogen produced by electrolysis enhanced the abundance of Methanobacterium and changed the methanogenesis pathway.


Subject(s)
Sewage , Electrolysis , Sewage/microbiology , Hydrogen Sulfide , Bioreactors/microbiology
16.
Chem Biodivers ; 20(7): e202300538, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37291995

ABSTRACT

Alpiniamides E-G, three previously unreported linear polyketide derivatives, along with two known compounds, were isolated from Streptomyces sp. QHA48, which was isolated from the saline lakes of Qinghai-Tibet Plateau. The structures of these compounds were determined through analysis of their spectroscopic data, as well as density functional theory prediction of NMR chemical shifts, application of the DP4+ algorithm and electronic circular dichroism (ECD) calculations. In a cell-based lipid-lowering assay, all five alpiniamides exhibited significant inhibition of lipid accumulation in HepG2 cells without inducing cytotoxic effects at a concentration of 27 µM.


Subject(s)
Lakes , Streptomyces , Streptomyces/chemistry , Circular Dichroism , Magnetic Resonance Spectroscopy , Lipids/pharmacology , Molecular Structure
17.
iScience ; 26(6): 106929, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37260746

ABSTRACT

Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe COVID-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in symptomatic patients with COVID-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14+ monocytes to induce inflammasomal cytokine/chemokine responses including IL1ß, IL8, and CCL2. Levels of ORF8 protein in the blood correlate with severity and disease-specific mortality in patients with acute SARS-CoV-2 infection. Furthermore, the ORF8-induced inflammasome response was readily inhibited by the NLRP3 inhibitor MCC950 in vitro. Our study identifies a dominant cause of pathogenesis, its underlying mechanism, and a potential new treatment strategy for severe COVID-19.

18.
RNA Biol ; 20(1): 334-347, 2023 01.
Article in English | MEDLINE | ID: mdl-37310201

ABSTRACT

Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.


Subject(s)
Psoriasis , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Circular/genetics , Psoriasis/genetics , Skin , Keratinocytes
19.
Biochim Biophys Acta Rev Cancer ; 1878(5): 188931, 2023 09.
Article in English | MEDLINE | ID: mdl-37315720

ABSTRACT

Peptide arginine deiminase 2(PAD2) catalyzes the conversion of arginine residues on target proteins to citrulline residues in the presence of calcium ions. This particular posttranslational modification is called citrullination. PAD2 can regulate the transcriptional activity of genes through histone citrullination and nonhistone citrullination. In this review, we summarize the evidence from recent decades and systematically illustrate the role of PAD2-mediated citrullination in tumor pathology and the regulation of tumor-associated immune cells such as neutrophils, monocytes, macrophages and T cells. Several PAD2-specific inhibitors are also presented to discuss the feasibility of anti-PAD2 therapy to treat tumors and the urgent problems to be solved. Finally, we review some recent developments in the development of PAD2 inhibitors.


Subject(s)
Citrullination , Protein Processing, Post-Translational , Humans , Citrulline/metabolism
20.
Heliyon ; 9(6): e17160, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37389073

ABSTRACT

Background: Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear. Methods: We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. Differentially expressed genes (DEGs) in AT2 were identified by the criteria |log2FC| ≥ 0.25 and P < 0.05 with DESeq2. A protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software to identify hub genes. We then constructed an ARDSp rat model through induction by lipopolysaccharide (LPS) airway instillation. Left lung RNA was extracted and sequenced via Illumina Hiseq platforms. Analysis of the rat RNA sequencing data was then used to verify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the identified hub genes. Results: In AT2, a total of 289 genes were identified as differentially expressed between those from ARDSp patients and healthy donors, and these included 190 upregulated and 99 downregulated genes. Ten hub genes were further identified (RPS27A, ACTG1, CAV1, HSP90AA1, HSPA5, CCND1, ITGA3, B2M, NEDD4L, and SEMA5A). There was a similar expression trend of HSPA5 between rat RNA and snRNA sequencing data. Discussion: ARDSp altered the gene expression profile of AT2. The identified hub genes were enriched in biological processes mainly involved in cell growth and transformation. Relatedly, ferroptosis and autophagy are possibly involved in AT2 injury during ARDSp. These novel insights into ARDSp may aid the discovery of potential targets for the diagnosis and treatment of ARDSp.

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