The application of organoids in colorectal diseases.

Intestinal organoids are a three-dimensional cell culture model derived from colon or pluripotent stem cells. Intestinal organoids constructed in vitro strongly mimic the colon epithelium in cell composition, tissue architecture, and specific functions, replicating the colon epithelium in an in vitro culture environment. As an emerging biomedical technology, organoid technology has unique advantages over traditional two-dimensional culture in preserving parental gene expression and mutation, cell function, and biological characteristics. It has shown great potential in the research and treatment of colorectal diseases. Organoid technology has been widely applied in research on colorectal topics, including intestinal tumors, inflammatory bowel disease, infectious diarrhea, and intestinal injury regeneration. This review focuses on the application of organoid technology in colorectal diseases, including the basic principles and preparation methods of organoids, and explores the pathogenesis of and personalized treatment plans for various colorectal diseases to provide a valuable reference for organoid technology development and application.

Size and morphology control over MOF-74 crystals.

Precise control of the size and morphology of metal-organic framework (MOF) crystals is challenging yet critical for the expansion of the application potential of MOF materials. This work presents a detailed investigation of the impact of various synthetic conditions such as reactant ratio, acidity, capping agent, reaction solution (H2O, ethanol and DMF) etc. on the size and morphology of Mg-MOF-74, a classical MOF with record high CO2 uptake capacity. By varying these fabrication parameters and modulators, the morphology and size of crystals can be precisely tuned in the nanometer to micrometer range. Particularly, the nanosized flaky Mg-MOF-74 crystals with an aspect ratio of ∼0.5 were synthesized for the first time by varying the amount of water. The MOF-74 crystals with different size and morphologies are good candidates for more advanced applications favored by crystal size and morphology control.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

CircABCB10 Promotes the Apoptosis and Inflammatory Response of 16HBE Cells by Cigarette Smoke Extract by Targeting miR-130a/PTEN Axis.

Background: Chronic obstructive pulmonary disease (COPD) has become a global public health problem due to its high mortality. So there is an urgent need to find an effective treatment. Methods: The targeting relationship among circABCB10, miR-130a and PTEN was predicted by the targetscan database (TargetScanHuman 8.0, https://www.targetscan.org/vert_80/). A total of 60 patients which were from the second affiliated hospital of Qiqihar Medical University from 2022 to 2023 were enrolled. The lung condition was detected by CT (Computed Tomography). The expression levels of circABCB10, miR-130a and PTEN in lung tissues were determined by qRT-PCR. The COPD model was established by stimulating normal and silenced 16HBE cells in circABCB10 genes with cigarette smoke extract (CSE) at different concentrations. qRT-PCR was conducted for the expression levels of circABCB10, miR-130a and PTEN, WB for the expression levels of apoptotic proteins, ELISA for the content of inflammatory factors, and CCK8 for the effect of CSE on the proliferation of cells. Results: CircABCB10 expression increased in lung tissues from patients with COPD and in 16HBE cells treated with CSE. The stimulation on cells with CSE increased the expression of inflammatory factors, while knocking down circABCB10 could reverse this response. The inflammatory response to the knockdown of circABCB10 was reversed by miR-130a inhibitor, which increased the expression of c-caspase 3. The targetscan database predicted the target factor downstream miR-130a was PTEN. Transfecting OE-PTEN reversed the inflammation of knocking down circABCB10, and increased the apoptosis and inflammation. Conclusion: CircABCB10 can cause the inflammatory response by targeting miR-130a/PTEN axis, which is a mechanism that may lead to the occurrence and development of COPD.

Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.

A Flexible Terahertz Metamaterial Sensor for Pesticide Sensing and Detection.

Terahertz (THz) waves have garnered significant interest across various fields, particularly in high-sensitivity sensing applications. Metamaterials can be employed in THz sensors, specifically for refractive index sensing and pesticide detection due to their high-sensitivity characteristics. In this Article, a dual-band flexible THz metamaterial sensor based on polyimide is proposed for refractive index and pesticide sensing, which is fabricated using ultraviolet (UV) lithography technology and measured by a THz time-domain spectroscope (TDS) system. The resonant frequencies of the sensor are at 0.37 and 1.13 THz, with transmission rates of 2.9% and 0.3%, respectively. With an analyte layer attached to the sensor's surface, the sensitivity of refractive index sensing can be calculated as 0.09 and 0.28 THz/RIU (refractive index unit) at the two resonant frequencies. In order to validate the exceptional pesticide sensing performance of the sensor, chlorpyrifos-methyl acetone solutions with various concentrations are added on it. Furthermore, a monolayer of graphene is coated on the sensor's surface, which is proved capable of improving pesticide sensing sensitivity at low concentrations due to strong π-π stacking interactions with π-electrons in chlorpyrifos-methyl solutions. Therefore, the graphene-coated sensor can be utilized in detecting pesticide solutions with low concentrations, and the sensor without graphene is preferred for high concentration detection. This work provides a novel option for the THz metamaterial sensor with high sensitivity covering a wide pesticide concentration range.

Low frequency magnetic field assisted production of acidic protease by Aspergillus niger.

Acid protease is widely used in industries such as food processing and feed additives. In the study, low frequency magnetic field (LF-MF) as an aid enhances acid protease production by Aspergillus niger (A. niger). The study assessed mycelial biomass, the enzymic activity of the acidic protease and underlying mechanism. At low intensities, alternating magnetic field (AMF) is more effective than static magnetic fields (SMF). Under optimal magnetic field conditions, acid protease activity and biomass increased by 91.44% and 16.31%, as compared with the control, respectively. Maximum 19.87% increase in enzyme activity after magnetic field treatment of crude enzyme solution in control group. Transcriptomics analyses showed that low frequency alternating magnetic field (LF-AMF) treatment significantly upregulated genes related to hydrolases and cell growth. Our results showed that low-frequency magnetic fields can enhance the acid protease production ability of A. niger, and the effect of AMF is better at low intensities. The results revealed that the effect of magnetic field on the metabolic mechanism of A. niger and provided a reference for magnetic field-assisted fermentation of A. niger.

Melatonin inhibits tongue squamous cell carcinoma: Interplay of ER stress-induced apoptosis and autophagy with cell migration.

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and ß-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

Carbon Dots Anchoring Single-Atom Pt on C3N4 Boosting Photocatalytic Hydrogen Evolution.

Carbon nitride (C3N4) has gained considerable attention and has been regarded as an ideal candidate for photocatalytic hydrogen evolution. However, its photocatalytic efficiency is still unsatisfactory due to the rapid recombination rate of photo-generated carriers and restricted surface area with few active sites. Herein, we successfully synthesized a single-atom Pt cocatalyst-loaded photocatalyst by utilizing the anchoring effect of carbon dots (CDs) on C3N4. The introduction of CDs onto the porous C3N4 matrix can greatly enhance the specific surface area of C3N4 to provide more surface-active sites, increase light absorption capabilities, as well as improve the charge separation efficiency. Notably, the functional groups of CDs can efficiently anchor the single-atom Pt, thus improving the atomic utilization efficiency of Pt cocatalysts. A strong interaction is formed via the connection of Pt-N bonds, which enhances the efficiency of photogenerated electron separation. This unique structure remarkably improves its H2 evolution performance under visible light irradiation with a rate of 15.09 mmol h-1 g-1. This work provides a new approach to constructing efficient photocatalysts by using CDs for sustainable hydrogen generation, offering a practical approach to utilizing solar energy for clean fuel production.

High-throughput sequencing-based analysis of the composition and diversity of the endophyte community in roots of Stellera chamaejasme.

Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.

Application of artificial intelligence-assisted image diagnosis software based on volume data reconstruction technique in medical imaging practice teaching.

BACKGROUND: In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching. METHODS: Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups. RESULTS: The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90). CONCLUSIONS: Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Improvement on wheat bread quality by in situ produced dextran-A comprehensive review from the viewpoint of starch and gluten.

Deterioration of bread quality, characterized by the staling of bread crumb, the softening of bread crust and the loss of aroma, has caused a huge food waste and economic loss, which is a bottleneck restriction to the development of the breadmaking industry. Various bread improvers have been widely used to alleviate the issue. However, it is noteworthy that the sourdough technology has emerged as a pivotal factor in this regard. In sourdough, the metabolic breakdown of carbohydrates, proteins, and lipids leads to the production of exopolysaccharides, organic acids, aroma compounds, or prebiotics, which contributes to the preeminent ability of sourdough to enhance bread attributes. Moreover, sourdough exhibits a "green-label" feature, which satisfies the consumers' increasing demand for additive-free food products. In the past two decades, there has been a significant focus on sourdough with in situ produced dextran due to its exceptional performance. In this review, the behaviors of bread crucial compositions (i.e., starch and gluten) during dough mixing, proofing, baking and bread storing, as well as alterations induced by the acidic environment and the presence of dextran are systemically summarized. From the viewpoint of starch and gluten, results obtained confirm the synergistic amelioration on bread quality by the coadministration of acidity and dextran, and also highlight the central role of acidification. This review contributes to establishing a theoretical foundation for more effectively enhancing the quality of wheat breads through the application of in situ produced dextran.

The effect of age, sex, and eastern cooperative oncology group performance status on the efficacy and safety of immune checkpoint inhibitors in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

Preserving Mesoporosity in Type III Porous Liquids through Dual-layer Surface Weaving.

The fundamental limitation for pore preservation in a Type III porous liquid (T3PL) is the need for a small aperture from the porous filler to realize size exclusion of a bulky solvent. We present a dual-layer surface weaving strategy that can disregard this limitation and achieve micro- and mesoporous metal-organic framework (MOF)-based T3PLs even with apertures much larger than the solvent molecules. By first weaving a tight network of poly(tert-butyl methacrylate) on the MOF surface, the poly(dimethylsiloxane) (PDMS) solvent can be effectively excluded from the pores while smaller guest molecules such as CO2, C2H4, and H2O can freely access the interior, as confirmed by low-pressure adsorption isotherms. Further application of a PDMS-containing polymer coating helps lower the viscosity of the PL due to increased particle dispersibility. This strategy has resulted in the successful construction of T3PLs with aperture sizes up to 3.1 nm.

Kaempferol alleviates adipose tissue inflammation and insulin resistance in db/db mice by inhibiting the STING/NLRP3 signaling pathway.

Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1ß, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.

Covalent polyphenols-proteins interactions in food processing: formation mechanisms, quantification methods, bioactive effects, and applications.

Proteins and polyphenols are abundant in the daily diet of humans and their interactions influence, among other things, the texture, flavor, and bioaccessibility of food. There are two types of interactions between them: non-covalent interactions and covalent interactions, the latter being irreversible and more powerful. In this review, we systematically summarized advances in the investigation of possible mechanism underlying covalent polyphenols-proteins interaction in food processing, effect of different processing methods on covalent interaction, methods for characterizing covalent complexes, and impacts of covalent interactions on protein structure, function and nutritional value, as well as potential bioavailability of polyphenols. In terms of health promotion of the prepared covalent complexes, health effects such as antioxidant, hypoglycemic, regulation of intestinal microbiota and regulation of allergic reactions have been summarized. Also, the possible applications in food industry, especially as foaming agents, emulsifiers and nanomaterials have also been discussed. In order to offer directions for novel research on their interactions in food systems, nutritional value, and health properties in vivo, we considered the present challenges and future perspectives of the topic.

Neoadjuvant immunotherapy based on PD-1/L1 inhibitors for gastrointestinal tumors: a review of the rationale and clinical advances.

The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses specific challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These findings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on specific treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efficacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research.

Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway.

BACKGROUND: Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. METHODS: In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. RESULTS: It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. CONCLUSIONS: Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.