Cytokinetic engineering enhances the secretory production of recombinant human lysozyme in Komagataella phaffii.

BACKGROUND: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. RESULTS: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. CONCLUSIONS: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.

Foreign body-intestinal canal angle guides management of ingested foreign bodies in the lower gastrointestinal tract.

BACKGROUND: Determining whether prompt surgery is required for patient with ingested foreign bodies is clinically important. PURPOSE: To evaluate the potential value of computed tomography (CT) in guiding the selection of surgical treatment for patients with ingested foreign bodies in the lower gastrointestinal tract. METHODS: Between January 2014 and December 2023, we analyzed the data of 58 patients (median age: 65.4 years; range, 31-96 years) with ingested foreign bodies in the lower gastrointestinal tract who underwent CT examinations. Patients were treated either conservatively (35 cases) or surgically (23 cases). The angle between the long axis of the foreign body and the intestinal canal (FB-IC angle) was measured. CT findings and clinical variables were evaluated to identify potential indicators for surgical treatment through univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis revealed the FB-IC angle (P = 0.002), presence of free peritoneal gas (P = 0.002), white blood cell count (P = 0.018), and neutrophil count (P = 0.007) as significant factors associated with surgical treatment. Multivariate analysis demonstrated that the FB-IC angle (odds ratio, 1.033; P = 0.045) and the presence of free peritoneal gas (odds ratio, 41.335; P = 0.002) are independent indicators for surgical management. The FB-IC angle showed an area under the receiver operating characteristic curve of 0.755, with a cutoff value of 51.25 degrees. CONCLUSION: The FB-IC angle and presence of free peritoneal gas serve as potential predictive imaging markers for surgical intervention.

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells' local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC. METHODS: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature. RESULTS: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster. CONCLUSIONS: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.

Effective capping of dissolved sulfide generated in Ulva prolifera-rich marine sediments by iron-rich red soil.

Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m2) before and immediately after pulsed macroalgal deposition (455 g/m2) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments.

On-chip multi-trap optical tweezers based on a guided wave-driven metalens.

Optical tweezer arrays (OTAs) have emerged as a powerful tool for quantum simulation, quantum computation, and quantum many-body physics. Conventional OTAs require bulky and costly optical components to generate multiple optical traps, such as spatial light modulators (SLMs). An integrated way to achieve on-chip OTAs is a sought-after goal for compact optical manipulation. In this Letter, we have numerically demonstrated compact on-chip multi-trap optical tweezers based on a guided wave-driven metalens. The presented on-chip optical tweezers are capable of capturing multiple polystyrene nanospheres in parallel. Moreover, we proposed an analytical design method to generate customized focal points from the integrated photonics chip into free space. Different trapping patterns are demonstrated to validate our proposed off-chip emission scheme. Our approach offers a promising solution to realize on-chip optical tweezers and provides a prospective way to realize elaborate emission control of guided waves into free-space beams.

Design and simulation of an extreme ultraviolet metalens based on the Pancharatnam-Berry phase.

Extreme ultraviolet (EUV) radiation plays a key role in the fields of material science, attosecond metrology, and lithography. However, the reflective optical components typically used in EUV systems contribute to their bulky size, weight, and increased costs for fabrication. In this paper, we theoretically investigate transmissive metalens designs capable of focusing the EUV light based on the Pancharatnam-Berry phase. The designed metalens is composed of nanoscale elliptical holes, which can guide and manipulate EUV light due to the higher refractive index of the vacuum holes compared to that of the surrounding material. We designed an EUV metalens with a diameter of 10 µm, which supports a focal length of 24 µm and a numerical aperture of up to 0.2. It can focus 55-nm EUV incident light to a diffraction-limited spot, and the focusing efficiency is calculated to be as high as about 7% over a broad EUV frequency range (50-65 nm). This study reveals the possibility of applying a dielectric metalens in the EUV region without a transmissive optical material.

Chelerythrine Chloride is an Affinity-Labeling Inactivator of CYP3A4 by Modification of Cysteine239.

Chelerythrine chloride (CHE) is a quaternary benzo[c]phenanthridine alkaloid with an iminium group that was found to cause time- and concentration-dependent inhibition of CYP3A4. The loss of CYP3A4 activity was independent of NADPH. CYP3A4 competitive inhibitor ketoconazole and nucleophile N-acetylcysteine (NAC) slowed the inactivation. No recovery of CYP3A4 activity was observed after dialysis. Dihydrochelerythrine hardly inhibited CYP3A4, suggesting that the iminium group was primarily responsible for the inactivation. UV spectral analysis revealed that the maximal absorbance of CHE produced a significant red-shift after being mixed with NAC, suggesting that 1,2-addition possibly took place between the sulfhydryl group of NAC and iminium group of CHE. Molecular dynamics simulation and site-direct mutagenesis studies demonstrated that modification of Cys239 by the iminium group of CHE attributed to the inactivation. In conclusion, CHE is an affinity-labeling inactivator of CYP3A4. The observed enzyme inactivation resulted from the modification of Cys239 of CYP3A4 by the iminium group of CHE.

Advances in mesenchymal stem cells therapy for tendinopathies.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Dihydrotanshinone I-Induced CYP1 Enzyme Inhibition and Alteration of Estradiol Metabolism.

Dihydrotanshinone I (DHTI) is a pharmacologically active component occurring in the roots of the herbal medicine Salvia miltiorrhiza Bunge. This study investigated DHTI-induced inhibition of CYP1A1, CYP1A2, and CYP1B1 with the aim to determine the potential effects of DHTI on the bioactivation of estradiol (E2), possibly related to preventive/therapeutic strategy for E2-associated breast cancer. Ethoxyresorufin as a specific substrate for CYP1s was incubated with human recombinant CYP1A1, CYP1A2, or CYP1B1 in the presence of DHTI at various concentrations. Enzymatic inhibition and kinetic behaviors were examined by monitoring the formation of the corresponding product. Molecular docking was further conducted to define the interactions between DHTI and the three CYP1s. The same method and procedure were employed to examine the DHTI-induced alteration of E2 metabolism. DHTI showed significant inhibition of ethoxyresorufin O-deethylation activity catalyzed by CYP1A1, CYP1A2 and CYP1B1 in a concentration-dependent manner (IC50 = 0.56, 0.44, and 0.11 µM, respectively). Kinetic analysis showed that DHTI acted as a competitive type of inhibitor of CYP1A1 and CYP1B1, whereas it noncompetitively inhibited CYP1A2. The observed enzyme inhibition was independent of NADPH and time. Molecular docking analysis revealed hydrogen bonding interactions between DHTI and Asp-326 of CYP1B1. Moreover, DHTI displayed preferential activity to inhibit 4-hydroxylation of E2 (a genotoxic pathway) mediated by CYP1B1. Exposure to DHTI could reduce the risk of genotoxicity induced by E2. SIGNIFICANCE STATEMENT: CYP1A1, CYP1A2, and CYP1B1 enzymes are involved in the conversion of estradiol (E2) into 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) through oxidation. 2-OHE2 is negatively correlated with breast cancer risk, and 4-OHE2 may be a significant initiator and promoter of breast cancer. The present study revealed that dihydrotanshinone I (DHTI) competitively inhibits CYP1A1/CYP1B1 and noncompetitively inhibits CYP1A2. DHTI exhibits a preference for inhibiting the genotoxicity associated with E2 4-hydroxylation pathway mediated by CYP1B1, potentially reducing the risk of 4-OHE2-induced genotoxicity.

Post-crotonylation oxidation by a monooxygenase promotes acetyl-CoA synthetase degradation in Streptomyces roseosporus.

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1-2), two new geranyl glucosides (3-4), and nine known compounds (5-13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Role of intelligent/interactive qualitative and quantitative analysis-three-dimensional estimated model in donor-recipient size mismatch following deceased donor liver transplantation.

BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

A fine recognition method of strawberry ripeness combining Mask R-CNN and region segmentation.

As a fruit with high economic value, strawberry has a short ripeness period, and harvesting at an incorrect time will seriously affect the quality of strawberries, thereby reducing economic benefits. Therefore, the timing of its harvesting is very demanding. A fine ripeness recognition can provide more accurate crop information, and guide strawberry harvest management more timely and effectively. This study proposes a fine recognition method for field strawberry ripeness that combines deep learning and image processing. The method is divided into three stages: In the first stage, self-calibrated convolutions are added to the Mask R-CNN backbone network to improve the model performance, and then the model is used to extract the strawberry target in the image. In the second stage, the strawberry target is divided into four sub-regions by region segmentation method, and the color feature values of B, G, L, a and S channels are extracted for each sub-region. In the third stage, the strawberry ripeness is classified according to the color feature values and the results are visualized. Experimental results show that with the incorporation of self-calibrated convolutions into the Mask R-CNN, the model's performance has been substantially enhanced, leading to increased robustness against diverse occlusion interferences. As a result, the final average precision (AP) has improved to 0.937, representing a significant increase of 0.039 compared to the previous version. The strawberry ripeness classification effect is the best on the SVM classifier, and the accuracy under the combined channel BGLaS reaches 0.866. The classification results are better than common manual feature extraction methods and AlexNet, ResNet18 models. In order to clarify the role of the region segmentation method, the contribution of different sub-regions to each ripeness is also explored. The comprehensive results demonstrate that the proposed method enables the evaluation of six distinct ripeness levels of strawberries in the complex field environment. This method can provide accurate decision support for strawberry refined planting management.

Development of a Chimeric Protein BiPPB-mIFNγ-tTßRII for Improving the Anti-Fibrotic Activity in Vivo by Targeting Fibrotic Liver and Dual Inhibiting the TGF-ß1/Smad Signaling Pathway.

Excessive production of transforming growth factor ß1 (TGF-ß1) in activated hepatic stellate cells (aHSCs) promotes liver fibrosis by activating the TGF-ß1/Smad signaling pathway. Thus, specifically inhibiting the pro-fibrotic activity of TGF-ß1 in aHSCs is an ideal strategy for treating liver fibrosis. Overexpression of platelet-derived growth factor ß receptor (PDGFßR) has been demonstrated on the surface of aHSCs relative to normal cells in liver fibrosis. Interferon-gamma peptidomimetic (mIFNγ) and truncated TGF-ß receptor type II (tTßRII) inhibit the TGF-ß1/Smad signaling pathway by different mechanisms. In this study, we designed a chimeric protein by the conjugation of (1) mIFNγ and tTßRII coupled via plasma protease-cleavable linker sequences (FNPKTP) to (2) PDGFßR-recognizing peptide (BiPPB), namely BiPPB-mIFNγ-tTßRII. This novel protein BiPPB-mIFNγ-tTßRII was effectively prepared using Escherichia coli expression system. The active components BiPPB-mIFNγ and tTßRII were slowly released from BiPPB-mIFNγ-tTßRII by hydrolysis using the plasma protease thrombin in vitro. Moreover, BiPPB-mIFNγ-tTßRII highly targeted to fibrotic liver tissues, markedly ameliorated liver morphology and fibrotic responses in chronic liver fibrosis mice by both inhibiting the phosphorylation of Smad2/3 and inducing the expression of Smad7. Meanwhile, BiPPB-mIFNγ-tTßRII markedly reduced the deposition of collagen fibrils and expression of fibrosis-related proteins in acute liver fibrosis mice. Furthermore, BiPPB-mIFNγ-tTßRII showed a good safety performance in both liver fibrosis mice. Taken together, BiPPB-mIFNγ-tTßRII improved the in vivo anti-liver fibrotic activity due to its high fibrotic liver-targeting potential and the dual inhibition of the TGF-ß1/Smad signaling pathway, which may be a potential candidate for targeting therapy on liver fibrosis.

Absorption enhancement in GaAs based quantum dot solar cells using double-sided nanopyramid arrays.

Quantum dot solar cells (QDSCs) are regarded as one of the most efficient devices due to their intermediate band structures. A suitable light-trapping (LT) strategy matching the absorption spectrum is important to improve the photocurrent conversion efficiency of QDSCs. In this paper, we have proposed a design of the periodically patterned top and bottom dielectric nanopyramid arrays for highly efficient light trapping in GaAs-based QDSCs. The dielectric nanopyramid arrays significantly improve the light absorption of QDSCs in the longer wavelength between 0.8 µm and 1.2 µm. In addition, this LT structure ensures a completely flat window layer and back surface field layer while passivating these semiconductor surfaces. For the optimized double-sided structure, the short-circuit current generated by QDSC is 34.32m A/c m 2, where the photocurrent from the quantum dots (QDs) is 5.17m A/c m 2. Compared to the photocurrent of the QDSC without an LT structure, the photocurrent of the double-sided structure is increased by 84%. The QD photocurrent of the double-sided structure is increased by 570% compared to that of the QDSC without the LT structure.

Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products in Streptomyces.

Streptomyces is renowned for its abundant production of bioactive secondary metabolites, but most of these natural products are produced in low yields. Traditional rational network refactoring is highly dependent on the comprehensive understanding of regulatory mechanisms and multiple manipulations of genome editing. Though random mutagenesis is fairly straightforward, it lacks a general and effective strategy for high throughput screening of the desired strains. Here in an antibiotic daptomycin producer S. roseosporus, we developed a dual-reporter system at the native locus of the daptomycin gene cluster. After elimination of three enzymes that potentially produce pigments by genome editing, a gene idgS encoding the indigoidine synthetase and a kanamycin resistant gene neo were integrated before and after the non-ribosomal peptidyl synthetase genes for daptomycin biosynthesis, respectively. After condition optimization of UV-induced mutagenesis, strains with hyper-resistance to kanamycin along with over-production of indigoidine were efficiently obtained after one round of mutagenesis and target screening based on the dual selection of the reporter system. Four mutant strains showed increased production of daptomycin from 1.4 to 6.4 folds, and significantly improved expression of the gene cluster. Our native-locus dual reporter system is efficient for targeting screening after random mutagenesis and would be widely applicable for the effective engineering of Streptomyces species and hyper-production of these invaluable natural products for pharmaceutical development.

Synthesis and Bioactivity Evaluation of Nepetaefolin F and Its Analogues.

Nepetaefolin F (5), an abietane diterpenoid, showed significant inhibitory activity against human cancer cells in vitro with an IC50 value of 6.3 µM. The syntheses of nepetaefolin F and its analogues are presented herein. The cytotoxicity against various cancer cell lines was evaluated; notably, the cyclopropanecarboxylate ester 42 displayed significant antitumor activity against MGC 803 cells with an IC50 value of 20.9 µM. Further studies revealed that 42 could upregulate the expression of p62, microtubule-associated protein 1 light-chain 3 ß (LC3 B-I), cleaved caspase-3, and cleaved caspase-9 and downregulate the expression of Beclin-1 and LC3B-II. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 42 could modulate multiple signaling pathways, especially for peroxisome proliferator-activated receptor (PPAR) and AMP-activated protein kinase (AMPK), which are closely related to autophagy. These results suggested that compound 42 is a promising lead by inhibiting cell proliferation and autophagy, as inducing cell apoptosis in MGC 803 cells.

Detection of Burkholderia pseudomallei with CRISPR-Cas12a based on specific sequence tags.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei), posing a significant threat to public health. Rapid and accurate detection of B. pseudomallei is crucial for preventing and controlling melioidosis. However, identifying B. pseudomallei is challenging due to its high similarity to other species in the same genus. To address this issue, this study proposed a dual-target method that can specifically identify B. pseudomallei in less than 40 min. We analyzed 1722 B. pseudomallei genomes to construct large-scale pan-genomes and selected specific sequence tags in their core genomes that effectively distinguish B. pseudomallei from its closely related species. Specifically, we selected two specific tags, LC1 and LC2, which we combined with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas12a) system and recombinase polymerase amplification (RPA) pre-amplification. Our analysis showed that the dual-target RPA-CRISPR/Cas12a assay has a sensitivity of approximately 0.2 copies/reaction and 10 fg genomic DNA for LC1, and 2 copies/reaction and 20 fg genomic DNA for LC2. Additionally, our method can accurately and rapidly detect B. pseudomallei in human blood and moist soil samples using the specific sequence tags mentioned above. In conclusion, the dual-target RPA-CRISPR/Cas12a method is a valuable tool for the rapid and accurate identification of B. pseudomallei in clinical and environmental samples, aiding in the prevention and control of melioidosis.

Sclareol attenuates liver fibrosis through SENP1-mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling.

Liver fibrosis is a key global health care burden. Sclareol, isolated from Salvia sclarea, possesses various biological activities. Its effect on liver fibrosis remains unknown. This study was proposed to evaluate the antifibrotic activity of sclareol (SCL) and explore its underlying mechanisms. Stimulated hepatic stellate cells served as an in vitro liver fibrosis model. The expression of fibrotic markers was assessed by western blot and real-time PCR. Two classical animal models, bile duct-ligated rats and carbon tetrachloride-treated mice, were utilized for the in vivo experiments. The liver function and fibrosis degree were determined by serum biochemical and histopathological analyses. VEGFR2 SUMOylation was analyzed using coimmunoprecipitation assay. Our results indicated that SCL treatment restricted the profibrotic propensity of activated HSCs. In fibrotic rodents, SCL administration alleviated hepatic injury and reduced collagen accumulation. Mechanistic studies indicated that SCL downregulated the protein level of SENP1 and enhanced VEGFR2 SUMOylation in LX-2 cells, which affected its intracellular trafficking. Blockade of the interaction between VEGFR2 and STAT3 was observed, resulting in the suppression of downstream STAT3 phosphorylation. Our findings demonstrated that SCL has therapeutic efficacy against liver fibrosis through mediating VEGFR2 SUMOylation, suggesting that SCL may be a potential candidate compound for its treatment.

Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells.

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes' aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.