Transplanting mitochondria from gastric epithelial cells reduces the malignancy of gastric cancer.

Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells.

Applications of ß-defensins against infectious pathogenic microorganisms.

INTRODUCTION: Antimicrobial peptides (AMPs) are polypeptides with potent antimicrobial activity against a broad range of pathogenic microorganisms. Unlike conventional antibiotics, AMPs have rapid bactericidal activity, a low capacity for inducing resistance, and compatibility with the host immune system. A large body of data supports the antimicrobial activities of a large body of data supports the antimicrobial activities of the class of AMPs known as ß-defensins. This review provides a comprehensive analysis of the effects of ß-defensins against various pathogenic microorganism: bacteria, fungi, viruses, Mycoplasmas and Chlamydiae. The primary mechanisms of ß-defensins against pathogenic microorganisms include inhibition of biofilms formations, dissolution of membranes, disruption of cell walls, and inhibition of adhesion and receptor binding. Although further study and structural modifications are needed, ß-defensins are promising candidates for antimicrobial therapy. AREAS COVERED: This review describes the inhibitory effects of ß-defensins on various pathogenic microorganisms. Additionally, we focus on elucidating the mechanisms underlying their actions to provide, providing valuable references for the further study of ß-defensins. EXPERT OPINION: The biological activities and modes of action of ß-defensins provide powerful resources for clinical microbial infection management. Addressing the salt sensitivity and toxicity of ß-defensins may further enhance their potential applications.

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

Quantification of volumetric thigh and paravertebral muscle fat content: comparison of quantitative Dixon (Q-Dixon) magnetic resonance imaging (MRI) with high-speed T2-corrected multiecho MR spectroscopy.

Background: Muscle fat infiltration (MFI) is increasingly recognized as a critical factor influencing muscle function and metabolic health. Accurate quantification of MFI is essential for diagnosing and monitoring various muscular and metabolic disorders. Quantitative Dixon (Q-Dixon) magnetic resonance imaging (MRI) and high-speed T2-corrected multi-echo (HISTO) magnetic resonance spectroscopy (MRS) are both advanced imaging techniques that offer potential for detailed assessment of MFI. However, the validity and reliability of these methods in measuring volumetric changes in muscle composition, particularly in both thigh and paravertebral muscles, have not been thoroughly compared. This study aims to validate volumetric measurements using Q-Dixon MRI against HISTO MRS in thigh and paravertebral muscles, taking into account the heterogeneity of MFI. Methods: A retrospective study was conducted with 54 subjects [mean age, 60 years; 38 male (M)/16 female (F)] for thigh muscle and 56 subjects (mean age, 50 years; 22 M/34 F) for paravertebral muscle assessment using a 3-Tesla MRI. The proton density fat fraction (PDFF) was measured with Q-Dixon MRI and HISTO MRS within the upper-middle part of quadriceps femoris and paravertebral muscles at L4/5 level in volumes-of-interest (VOIs). The corresponding volumetric Q-Dixon freehand VOI PDFF was measured. Scatterplots, Bland-Altman plots, Spearman correlation coefficients, and Wilcoxon signed rank test with Bonferroni correction were employed. The Kruskal-Wallis H tests followed by Bonferroni-corrected post hoc tests were analyzed to compare parameter differences with visual MFI grades. Results: Q-Dixon cubic VOI PDFF correlated positively with HISTO MRS PDFF in thigh (r=0.96, P<0.001) and paravertebral groups (r=0.98, P<0.001), with insignificant differences (P=0.29, 0.82, respectively). Both PDFF values from cubic VOIs in Q-Dixon and HISTO MRS differed from the freehand Q-Dixon PDFF (all P<0.001). Only for <5% HISTO MRS PDFF, there was a difference between HISTO MRS PDFF and Q-Dixon cubic VOI PDFF (P=0.002). Conclusions: Volumetric Q-Dixon cubic VOI PDFF exhibited good correlation and consistency with HISTO MRS PDFF for quantitative fat assessment in thigh and paravertebral muscles except for muscles with fat fraction <5%, and the Q-Dixon freehand VOI PDFF offers a more comprehensive assessment of the actual MFI compared to cubic VOI.

Novel goose parvovirus VP1 targets IRF7 protein to block the type I interferon upstream signaling pathway.

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-ß induction. NGPV impedes the expression of IFN-ß and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-ß induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-ß expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-ß, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.

Association of plasma microRNA-16-5p and abdominal aortic calcification in maintenance hemodialysis patients.

Recent studies have shown that microRNA-16-5p (miR-16-5p) plays a crucial role in the pathological mechanism of vascular calcification. Nevertheless, the expression profile of miR-16-5p in maintenance hemodialysis (MHD) patients who are predisposed to vascular calcification remains unknown. This study aims to investigate the potential associations between calcification risk and serum miR-16-5p expression among MHD patients. This cross-sectional study involved 132 MHD patients from the Dialysis Center of Beijing Friendship Hospital between 1 January 2019 and 31 December 2020. The degree of calcification in MHD patients was assessed using the Abdominal aortic calcification (AAC) score, and miR-16-5p expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) with the 2-ΔΔCT method. Statistical analyses, including spearman correlation, linear regression and logistic regression analysis were used to explore the associations between laboratory parameters and AAC score. Calcifications were observed in 79(59.80%) patients. The linear regression showed a one-quartile decrease in miR-16-5p expression led to a significant increase in the AAC score by 5.336 (95% CI: 2.670-10.662, p = 0.000). Multivariate logistic regression analyses revealed that decreased miR-16-5p expression, reduced serum urea nitrogen, elevated white blood cell count, and longer dialysis vintage were significantly associated with an increased incidence of vascular calcification. The Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) of the miR-16-5p-based logistic regression model was 0.842 (95% CI: 0.771-0.913, p = 0.000). There was an independent association between miR-16-5p expression and calcification degree. Lower miR-16-5p expression levels seem to be a potential risk factor of vascular calcification in MHD patients.

Enhanced multi view 3D reconstruction with improved MVSNet.

Although 3D reconstruction has been widely used in many fields as a key component of environment perception, existing technologies still have the potential for further improvement in 3D scene reconstruction. We propose an improved reconstruction algorithm based on the MVSNet network architecture. To glean richer pixel details from images, we suggest deploying a DE module integrated with a residual framework, which supplants the prevailing feature extraction mechanism. The DE module uses ECA-Net and dilated convolution to expand the receptive field range, performing feature splicing and fusion through the residual structure to retain the global information of the original image. Moreover, harnessing attention mechanisms refines the 3D cost volume's regularization process, bolstering the integration of information across multi-scale feature volumes, consequently enhancing depth estimation precision. When assessed our model using the DTU dataset, findings highlight the network's 3D reconstruction scoring a completeness (comp) of 0.411 mm and an overall quality of 0.418 mm. This performance is higher than that of traditional methods and other deep learning-based methods. Additionally, the visual representation of the point cloud model exhibits marked advancements. Trials on the Blended MVS dataset signify that our network exhibits commendable generalization prowess.

Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.

Age-related dopamine (DA) neuron loss is a primary feature of Parkinson's disease. However, it remains unclear whether similar biological processes occur during healthy aging, albeit to a lesser degree. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans. In mice, we identified no changes in midbrain neuron numbers throughout aging. Despite this, we found age-related decreases in midbrain mRNA expression of tyrosine hydroxylase (Th), the rate limiting enzyme of DA synthesis. Among midbrain glutamatergic cells, we similarly identified age-related declines in vesicular glutamate transporter 2 (Vglut2) mRNA expression. In co-transmitting Th +/Vglut2 + neurons, Th and Vglut2 transcripts decreased with aging. Importantly, striatal Th and Vglut2 protein expression remained unchanged. In translating our findings to humans, we found no midbrain neurodegeneration during aging and identified age-related decreases in TH and VGLUT2 mRNA expression similar to mouse. Unlike mice, we discovered diminished density of striatal TH+ dopaminergic terminals in aged human subjects. However, TH and VGLUT2 protein expression were unchanged in the remaining striatal boutons. Finally, in contrast to Th and Vglut2 mRNA, expression of most ribosomal genes in Th + neurons was either maintained or even upregulated during aging. This suggests a homeostatic mechanism where age-related declines in transcriptional efficiency are overcome by ongoing ribosomal translation. Overall, we demonstrate species-conserved transcriptional effects of aging in midbrain dopaminergic and glutamatergic neurons that are not accompanied by marked cell death or lower striatal protein expression. This opens the door to novel therapeutic approaches to maintain neurotransmission and bolster neuronal resilience.

Giant Anisotropic Thermal Expansion Phase Transition of Silver Iodide Anionic Organic-Inorganic Hybrid.

Hybrid metal halide materials with charming phase transition behaviors have attracted considerable attention. In former works, much attention has been focused on the phase transition triggered by the order-disorder or displacement motions of the organic component. However, manipulating the variation of the inorganic component to achieve the phase transition has rarely been reported. Herein, two novel organic-inorganic hybrid materials, [THPM]n[AgX2]n (THPM = 3,4,5,6-tetrahydropyrimidin-1-ium, X = I for 1 and Br for 2) with the [AgX2]nn- anionic chain structure, were synthesized. At 293 K, the [AgX2]nn- chains in 1 were constructed by the tetramer units of Ag atoms, while that in 2 was assembled by the dimer structure. Upon heating to 355 K, owing to the variation of the metallophilic interaction between adjacent Ag atoms, a unique transformation process from tetramer to dimer in [AgI2]nn- chains of 1 can be detected and endow 1 with a giant anisotropic thermal expansion with linear strain of ∼7% and shear strain of ∼20%, which can be used as a mechanical actuator for switching. Alternatively, for 2, no phase transition process can be observed upon the temperature variation. This work provides an effective approach to design phase transition materials triggered by the inorganic part.

Simple, and highly efficient edge-effect surface acoustic wave atomizer.

Conventional surface acoustic wave (SAW) atomizers require a direct water supply on the surface, which can be complex and cumbersome. This paper presents a novel SAW atomizer that uses lateral acoustic wetting to achieve atomization without a direct water supply. The device works by simply pressing a piece of wetted paper strip against the bottom of an excited piezoelectric transducer. The liquid then flows along the side to the unmodified surface edge, where it is atomized into a well-converging mist in a stable and sustainable manner. We identified this phenomenon as the edge effect, using numerical simulation results of surface displacement mode. The feasibility of the prototype design was demonstrated by observing and investigating the integrated process of liquid extraction, transport, and atomization. We further explored the hydrodynamic principles of the change and breakup in liquid film geometry under different input powers. Experiments demonstrate that our atomizer is capable of generating high-quality fine liquid particles stably and rapidly even at very high input power. Compared to conventional SAW atomizer, the dispersion of mist width can be scaled down by 70%, while the atomization rate can be increased by 37.5%. Combined with the advantages of easy installation and robustness, the edge effect-based atomizer offers an attractive alternative to current counterparts for applications requiring high efficiency and miniaturization, such as simultaneous synthesis and encapsulation of nanoparticles, pulmonary drug delivery and portable inhalation therapy.

Characterization and efficacy of C60 nano-photosensitive drugs in colorectal cancer treatment.

BACKGROUND: Fullerenes C60 shows great potential for drug transport. C60 generates large amounts of singlet oxygen upon photoexcitation, which has a significant inhibitory effect on tumor cells, so the photosensitive properties of C60 were exploited for photodynamic therapy of tumors by laser irradiation. METHODS: In this study, C60-NH2 was functionalized by introducing amino acids on the surface of C60, coupled with 5-FU to obtain C60 amino acid-derived drugs (C60AF, C60GF, C60LF), and activated photosensitive drugs (C60AFL, C60GFL, C60LFL) were obtained by laser irradiation. The C60 nano-photosensitive drugs were characterized in various ways, and the efficacy and safety of C60 nano-photosensitive drugs were verified by cellular experiments and animal experiments. Bioinformatics methods and cellular experiments were used to confirm the photosensitive drug targets and verify the therapeutic targets with C60AF. RESULTS: Photosensitised tumor-targeted drug delivery effectively crosses cell membranes, leads to more apoptotic cell death, and provides higher anti-tumor efficacy and safety in vitro and in vivo colorectal cancer pharmacodynamic assays compared to free 5-FU.C60 photosensitized drug promotes tumor killing by inhibiting the colorectal cancer FLOR1 tumor protein target, with no significant toxic effects on normal organs. CONCLUSION: C60 photosensitized drug delivery systems are expected to improve efficacy and reduce side effects in the future treatment of colorectal cancer. Further and better development and design of drugs and vectors for colorectal cancer therapy.

Follicular fluid meiosis-activating sterol prevents porcine ovarian granulosa cells from hypoxia-induced apoptosis via inhibiting STAT4 expression.

Follicular fluid meiosis-activating sterol (FF-MAS) is a small molecule compound found in FF, named for its ability to induce oocyte resumption of meiosis. Granulosa cells (GCs) within the follicle are typically located in a hypoxic environment under physiologic conditions due to limited vascular distribution. Previous research suggests that hypoxia-induced cell cycle arrest and apoptosis in GCs may be crucial triggering factors in porcine follicular atresia. However, the impact of FF-MAS on GCs within follicles has not been explored so far. In this study, we uncovered a novel role of FF-MAS in facilitating GC survival under hypoxic conditions by inhibiting STAT4 expression. We found that STAT4 expression was upregulated in porcine GCs exposed to 1% O2. Both gain and loss of function assays confirmed that STAT4 was required for cell apoptosis under hypoxia conditions, and that the GC apoptosis caused by hypoxia was markedly attenuated following FF-MAS treatment through inhibition of STAT4 expression. Correlation analysis in vivo revealed that GC apoptosis was associated with increased STAT4 expression, while the FF-MAS content in follicular fluid was negatively correlated with STAT4 mRNA levels and cell apoptosis. These findings elucidate a novel role of FF-MAS-mediated protection of GCs by inhibiting STAT4 expression under hypoxia, which might contribute to the mechanistic understanding of follicular development.

Granulosa cells (GCs) influence follicle growth and development, with their proliferation and differentiation promoting follicle development and ovulation, while their programmed cell death and degeneration trigger follicular atresia. In this study, to investigate the effect of FF-MAS on GCs of follicles, we performed gene expression profiling in the domestic pig (Sus scrofa). We discovered STAT4 is required for GC apoptosis under hypoxia conditions both in vitro and in vivo and FF-MAS prevents porcine ovarian granulosa cells from hypoxia-induced apoptosis via inhibiting STAT4 expression.

Unveiling the Novel Benefits of Co-Administering Butyrate and Active Vitamin D3 in Mice Subjected to Chemotherapy-Induced Gut-Derived Pseudomonas aeruginosa Sepsis.

Cancer patients face increased susceptibility to invasive infections, primarily due to ulcerative lesions on mucosal surfaces and immune suppression resulting from chemotherapy. Pseudomonas aeruginosa (P. aeruginosa) bacteremia is notorious for its rapid progression into fatal sepsis, posing a significant threat to cancer patients, particularly those experiencing chemotherapy-induced neutropenia. This bacterial infection contributes significantly to morbidity and mortality rates among such individuals. Our latest report showed the mutually beneficial effects of postbiotic butyrate on 1,25-dihydroxyvitamin D3 (1,25D3)-controlled innate immunity during Salmonella colitis. Hence, we investigated the impact of butyrate and 1,25D3 on chemotherapy-induced gut-derived P. aeruginosa sepsis in mice. The chemotherapy-induced gut-derived P. aeruginosa sepsis model was established through oral administration of 1 × 107 CFU of the P. aeruginosa wild-type strain PAO1 in C57BL/6 mice undergoing chemotherapy. Throughout the infection process, mice were orally administered butyrate and/or 1,25D3. Our observations revealed that the combined action of butyrate and 1,25D3 led to a reduction in the severity of colitis and the invasion of P. aeruginosa into the liver and spleen of the mice. This reduction was attributed to an enhancement in the expression of defensive cytokines and antimicrobial peptides within the cecum, coupled with decreased levels of zonulin and claudin-2 proteins in the mucosal lining. These effects were notably more pronounced when compared to treatments administered individually. This study unveils a promising alternative therapy that involves combining postbiotics and 1,25D3 for treating chemotherapy-induced gut-derived P. aeruginosa sepsis.

Building Co16-N3-Based UiO-MOF to Expand Design Parameters for MOF Photosensitization.

The construction of secondary building units (SBUs) in versatile metal-organic frameworks (MOFs) represents a promising method for developing multi-functional materials, especially for improving their sensitizing ability. Herein, we developed a dual small molecules auxiliary strategy to construct a high-nuclear transition-metal-based UiO-architecture Co16-MOF-BDC with visible-light-absorbing capacity. Remarkably, the N3 - molecule in hexadecameric cobalt azide SBU offers novel modification sites to precise bonding of strong visible-light-absorbing chromophores via click reaction. The resulting Bodipy@Co16-MOF-BDC exhibits extremely high performance for oxidative coupling benzylamine (~100 % yield) via both energy and electron transfer processes, which is much superior to that of Co16-MOF-BDC (31.5 %) and Carboxyl @Co16-MOF-BDC (37.5 %). Systematic investigations reveal that the advantages of Bodipy@Co16-MOF-BDC in dual light-absorbing channels, robust bonding between Bodipy/Co16 clusters and efficient electron-hole separation can greatly boost photosynthesis. This work provides an ideal molecular platform for synergy between photosensitizing MOFs and chromophores by constructing high-nuclear transition-metal-based SBUs with surface-modifiable small molecules.

The relationships between motor skills and executive functions in children with and without autism spectrum disorder.

To date, information on associations between motor skills and executive functions (EF) in autistic children is limited. The purpose of this study was to compare motor skills and EF performance between autistic children and typically developing (TD) children and to examine the relationships between motor skills and EF in these two groups. Forty-eight autistic children and 48 TD children aged 6 to 12 years were recruited for this study. Motor skills were measured with the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). EF was assessed with the Stroop Color and Word Test, the Wisconsin Card Sorting Task (WCST), and the Test of Attentional Performance: Go/No-go test. Independent sample t-tests were used to compare the BOT-2 scores and EF measures between autistic children and TD children. Pearson product-moment correlation and regressions were conducted to assess the relationships between the BOT-2 scores and the EF measures for each group. Results showed that autistic children scored significantly lower than TD children on all four BOT-2 composite scores and a total motor composite. Autistic children also demonstrated significantly lower levels of performance on all EF measures than TD children. Further, autistic children showed more significant associations between motor skills and EF than TD children, particularly pronounced in the domains of fine manual control and manual coordination to cognitive flexibility, as well as manual coordination and inhibitory control. Continued development of motor skills and EF in autistic children is important. The relationships between motor skills and EF were significant among autistic children, suggesting future research on promoting EF through motor skill interventions in autistic children is required.

Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross-sectional study with 2020 participants.

BACKGROUND: With the decline of cognitive function in vascular cognitive impairment, the burden on the family and society will increase. Therefore, early identification of vascular mild cognitive impairment (VaMCI) is crucial. The focus of early identification of VaMCI is on the attention of risk factors. Therefore, this study aimed to investigate the relationship between diabetes and VaMCI among the Chinese, hoping to predict the risk of VaMCI by diabetes and to move the identification of vascular cognitive impairment forward. METHODS: We collected data from seven clinical centers and nine communities in China. All participants were over 50 years of age and had cognitive complaints. We collected basic information of the participants, and cognitive function was professionally assessed by the Montreal Cognitive Assessment scale. Finally, logistic regression analysis was used to analyze the correlation between each factor and VaMCI. RESULTS: A total of 2020 participants were included, including 1140 participants with VaMCI and 880 participants with normal cognition. In univariate logistic regression analysis, age, heavy smoking, and diabetes had a positive correlation with VaMCI. At the same time, being married, high education, and light smoking had a negative correlation with VaMCI. After correction, only diabetes (OR = 1.04, 95% CI: 1.01-1.09, p = 0.05) had a positive correlation with VaMCI, and high education (OR = 0.60, 95% CI:.45-.81, p = 0.001) had a negative correlation with VaMCI. CONCLUSION: In our study, we found that diabetes had a positive correlation with VaMCI, and high education had a negative correlation with VaMCI. Therefore, early identification and timely intervention of diabetes may reduce the risk of VaMCI and achieve early prevention of VaMCI.

Resveratrol inhibits arecoline-induced fibrotic properties of buccal mucosal fibroblasts via miR-200a activation.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

Advances in the differentiation of pluripotent stem cells into vascular cells.

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

Biological factors driving colorectal cancer metastasis.

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

When will the immune-stimulating antibody conjugates (ISACs) be transferred from bench to bedside?

Immunostimulatory antibody conjugates (ISACs) as a promising new generation of targeted therapeutic antibody-drug conjugates (ADCs), that not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. However, several ISACs are still in the early stages of clinical development or have already failed. Therefore, it is crucial to design ISACs more effectively to overcome their limitations, including high toxicity, strong immunogenicity, long development time, and poor pharmacokinetics. This review aims to summarize the composition and function of ISACs, incorporating current design considerations and ongoing clinical trials. Additionally, the review delves into the current issues with ISACs and potential solutions, such as adjusting the drug-antibody ratio (DAR) to improve the bioavailability of ISACs. By leveraging the affinity and bioavailability-enhancing properties of bispecific antibodies, the utility between antibodies and immunostimulatory agents can be balanced. Commonly used immunostimulatory agents may induce systemic immune reactions, and BTK (Bruton's tyrosine kinase) inhibitors can regulate immunogenicity. Finally, the concept of grafting ADC's therapeutic principles is simple, but the combination of payload, linker, and targeted functional molecules is not a simple permutation and combination problem. The development of conjugate drugs faces more complex pharmacological and toxicological issues. Standing on the shoulders of ADC, the development and application scenarios of ISAC are endowed with broader space.