[Ergosterol peroxide inducing apoptosis of human hepatocellular carcinoma by regulating mitochondrial apoptosis pathway].

This study aims to investigate the effect of ergosterol peroxide(EP) on the apoptosis of human hepatocellular carcinoma and its mechanism of action. The cell viability of HepG2 and SK-Hep-1 cells with 0(blank control), 2.5, 5, 10, 20, 40, and 80 µmol·L~(-1) of EP after 24, 48, and 72 h of action was detected by using CCK-8 assay, and the half inhibitory concentrations(IC_(50)) at 24, 48, and 72 h were calculated. Formal experiments were performed to detect the effect of EP on intracellular reactive oxygen species(ROS) using DCFH-DA staining, the effect of EP on intracellular mitochondrial membrane potential using JC-1 staining, the number of apoptotic cells using Annexin V-FITC/PI double-staining after HepG2 cells were co-cultured with 0(blank control), 10, 20, 40 µmol·L~(-1) EP for 48 h. The effects of EP at different concentrations on apoptotic morphology were detected using AO/EB staining. The effects of different concentrations of EP on the protein expression of mitochondrial apoptosis pathway-related proteins B cell lymphoma 2(Bcl-2), cytochrome C(Cyt-C), Bcl-2-related X protein(Bax), caspase-3, cleaved caspase-3, caspase-9, and cleaved caspase-9 were examined by using Western blot. The results showed that different concentrations of EP could inhibit the proliferation of hepatocellular carcinoma with concentration-and time-dependent trends. Compared with the blank control group, the ROS level in the EP-treated group increased significantly(P<0.05). The mitochondrial membrane potential decreased significantly(P<0.05). The total apoptosis rate increased significantly(P<0.05). The expression of Bcl-2 protein was significantly down-regulated, and the expression of Cyt-C, Bax, cleaved caspase-9, and cleaved caspase-3 were significantly up-regulated(P<0.05). In summary, EP may inhibit the proliferation of hepatocellular carcinoma by modulating the mitochondria-mediated apoptosis pathway and induce apoptosis.

[Mechanism of ergosterol peroxide on MCF-7 breast cancer cells based on network pharmacology and in vitro experiments].

This study investigated the effects of ergosterol peroxide(EP) on the proliferation and apoptosis of MCF-7 breast cancer cells, explored its possible mechanisms of action, and verified the effects and mechanisms by in vitro experiments. Network pharmaco-logy was used to screen the target proteins of EP and construct target networks and protein-protein interaction(PPI) networks to predict the potential target proteins and related pathways involved in EP anti-breast cancer effects. The MTT assay was performed to measure the inhibitory effect of EP on MCF-7 cell proliferation, and the colony formation assay was used to assess the cell cloning ability. Flow cytometry and laser confocal microscopy were employed to evaluate cell apoptosis, mitochondrial membrane potential and reactive oxygen species(ROS) levels. Western blot analysis was conducted to examine the expression levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), caspase-7, cleaved caspase-7, phosphatidylinositol 3-kinase(PI3K), and se-rine/threonine kinase B(AKT) in MCF-7 cells treated with EP. The results of network pharmacology prediction yielded 173 common targets between EP and breast cancer; the results of Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis showed that EP treatment for breast cancer mainly affected the signaling pathways such as cancer pathway, PI3K-AKT signaling pathway, cellular senescence signaling pathway, and viral carcinogenesis pathway; and the MTT assay results showed that the viability of MCF-7 cells in the EP group was significantly lower than that in the control group, exhibiting a time-and concentration-dependent trend, and EP can inhibit colony formation of MCF-7 breast cancer cells. Treatment with 10, 20, and 40 µmol·L~(-1) EP for 24 h resulted in a significant increase in the total apoptosis rate of MCF-7 cells, a significant decrease in mitochondrial membrane potential, and a significant increase in ROS levels. In addition, treatment with EP led to an upregulation of Cyt C, Bax, and cleaved caspase-7 protein expression, and a downregulation of p-PI3K, p-AKT, and Bcl-2 protein expression in MCF-7 cells. Studies have shown that EP inhibits MCF-7 breast cancer cell proliferation and reduces colony formation by a mechanism that may be related to the PI3K-AKT pathway mediating the mitochondrial apoptotic pathway.

Local Mechanical Modulation-Driven Evagination in Invaginated Epithelia.

Local cells can actively create reverse bending (evagination) in invaginated epithelia, which plays a crucial role in the formation of elaborate organisms. However, the precise physical mechanism driving the evagination remains elusive. Here, we present a three-dimensional vertex model, incorporating the intrinsic cell polarity, to explore the complex morphogenesis induced by local mechanical modulations. We find that invaginated tissues can spontaneously generate local reverse bending due to the shift of the apicobasal polarity. Their exact shapes can be analytically determined by the local apicobasal differential tension and the internal stress. Our continuum theory exhibits three regions in a phase diagram controlled by these two parameters, showing curvature transitions from ordered to disordered states. Additionally, we delve into epithelial curvature transition induced by the nucleus repositioning, revealing its active contribution to the apicobasal force generation. The uncovered mechanical principles could potentially guide more studies on epithelial folding in diverse systems.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Does transanal drainage tubes placement have an impact on the incidence of anastomotic leakage after rectal cancer surgery? a systematic review and meta-analysis.

BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence. METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery. RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively). CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis. TRIAL REGISTRATION: PROSPERO: CRD42023427914.

Association between tea consumption and colorectal cancer: a systematic review and meta-analysis of a population-based study.

PURPOSE: A meta-analysis study was performed to systematically assess the association between tea consumption and CRC risk. METHODS: Cochrane Library, Embase, PubMed, and Web of Science were retrieved to collect articles in English since 24 July 2023. Databases were searched and evaluated by two reviewers independently.We screened the literature based on inclusion and exclusion criteria. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: We included fourteen articles in this meta-analysis. We analyzed the data using a random effect model to explore the association between tea consumption and CRC because of apparent heterogeneity (P < 0.001, I2 = 99.5%). The combined results of all tests showed that there is no statistically significant association between tea consumption and CRC risk (OR = 0.756, 95%CI = 0.470-1.215, P = 0.247). Subsequently, subgroup analysis and sensitivity analysis were performed. Excluding any single study, the overall results ranged from 0.73 (95%CI = 0.44-1.20) to 0.86 (95%CI = 0.53-1.40). It was determined that there was no significant publication bias between tea consumption and CRC risk (P = 0.064) by Egger's tests. CONCLUSIONS: The results indicated that tea consumption may not be significantly associated with the development of CRC. IMPLICATIONS OF KEY FINDINGS: Tea reduces colon cancer risk by 24%, but the estimate is uncertain. The actual effect on risk can range from a reduction of 51% to an increase of 18%, but regional and population differences may cause differences.

Establishment of clinical predictive model based on the study of influence factors in patients with colorectal polyps.

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is generally thought to be caused by the transformation of colorectal polyps. It has been shown that early detection and removal of colorectal polyps may reduce the mortality and morbidity of colorectal cancer. Objective: Based on the risk factors associated with colorectal polyps, an individualized clinical prediction model was built to predict and evaluate the possibility of developing colorectal polyp. Methods: A case-control study was conducted. Clinical data were collected from 475 patients who underwent colonoscopy at the Third Hospital of Hebei Medical University from 2020 to 2021. All clinical data were then divided into training sets and validation sets by using R software (7:3). A multivariate logistic analysis was performed to identify the factors associated with colorectal polyps according to the training set, and a predictive nomogram was created by R software based on the multivariate analysis. The results were internally validated by receiver operating characteristic (ROC) curves, calibration curves, and externally validated by validation sets. Results: Multivariate logistic regression analysis showed that age (OR = 1.047, 95% CI = 1.029-1.065), history of cystic polyp (OR = 7.596, 95% CI = 0.976-59.129), and history of colorectal diverticulums (OR = 2.548, 95% CI = 1.209-5.366) were independent risk factors for colorectal polyps. History of constipation (OR = 0.457, 95% CI = 0.268-0.799) and fruit consumption (OR = 0.613, 95% CI 0.350-1.037) were protective factors for colorectal polyps. The nomogram demonstrated good accuracy for predicting colorectal polyps, with both C index and AUC being 0.747 (95% CI = 0.692-0.801). The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes. Both internal and external validation of the model showed good results. Conclusion: In our study, the nomogram prediction model is reliable and accurate, which can help early clinical screening of patients with high-risk colorectal polyps, improve polyp detection rate, and reduce the incidence of colorectal cancer (CRC).

Pancreatitis and Pancreatic Cancer Risk.

Purpose: The present retrospective study aimed to explore the relationship between pancreatitis and pancreatic cancer in the population cohort of the UK Biobank (UKB) (https://www.ukbiobank.ac.uk). Methods: From the 500 thousand population cohort of UKB, according to the age and gender of patients with pancreatic cancer 1:10, matching the control without pancreatic cancer, the binary Logistic regression model was used to analyze the relationship between pancreatitis and pancreatic cancer, and subgroup analyses were used to identify potential effect modifiers. Results: A total of 1538 patients with pancreatic cancer were compared with 15 380 controls. In the fully adjusted model, patients with pancreatitis had a significantly increased risk of pancreatic cancer compared with no pancreatitis. The risk of pancreatitis and pancreatic cancer increased with the age of pancreatitis, and the risk of pancreatic cancer was highest in the 61 to 70 age group. In addition, in the first 3 years of acute pancreatitis, the risk of pancreatic cancer increased significantly with the increase in the duration of the disease (odds ratio [OR] 29.13, 95% confidence interval [CI]: 16.34-51.93), after 3 years, the trend of increase decreased. After more than 10 years, there was no significant correlation between the risk of acute pancreatitis and pancreatic cancer. However, patients with chronic pancreatitis were significantly associated with an increased risk of pancreatic cancer only in the first 3 years (OR 28.14, 95% CI: 14.86-53.31). Conclusion: Pancreatitis may associate with an increased risk of pancreatic cancer. The older the age of pancreatitis, the higher the risk of pancreatic cancer. The risk of pancreatic cancer increases significantly in the first 3 years of the course of pancreatitis. This may provide an alternative strategy for the early identification of individuals at high risk of pancreatic cancer.

Coptis, Pinellia, and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer. AIM: To identify efficient therapeutic agents or strategies that can treat H. pylori infection. METHODS: We performed literature analysis, experimental validation, and network pharmacology. First, traditional Chinese medicine (TCM) prescriptions for the treatment of H. pylori infection were obtained from the China National Knowledge Infrastructure, China Biology Medicine, China Science and Technology Journal Database, and WanFang databases. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). Next, we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions. Then, an H. pylori-associated chronic mouse model of gastritis was established. The antibacterial properties and anti-inflammatory potential of the core drug combination were evaluated by the rapid urease test, modified Warthin-Starry silver staining, histopathological analysis, and enzyme linked immunosorbent assay. Finally, the active compounds, hub targets, and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology. RESULTS: The TCM treatment of H. pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing, bitter descending, cold and warm drugs. The combination of Coptis, Pinellia, and Scutellaria (CPS) was identified as the core drug combination from 207 prescriptions and 168 herbs. This drug combination eradicated H. pylori, alleviated the gastric pathology induced by H. pylori infection, and reduced the expression levels of tumor necrosis factor-α (P = 0.024) and interleukin-1ß (P = 0.001). Moreover, a total of 35 compounds and 2807 targets of CPS were identified using online databases. Nine key compounds (tenaxin I, neobaicalein, norwogonin, skullcapflavone II, baicalein, 5,8,2'-trihydroxy-7-methoxyflavone, acacetin, panicolin, and wogonin) and nine hub target proteins (EGFR, PTGS2, STAT3, MAPK3, MAPK8, HSP90AA1, MAPK1, MMP9, and MTOR) were further explored. Seventy-seven signaling pathways were correlated with H. pylori-induced inflammation and carcinogenesis. CONCLUSION: In summary, we showed that CPS is the core drug combination for treating H. pylori infection. Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa. Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multi-pathway regulatory mechanisms. Although the results derived from network pharmacology are not necessarily comprehensive, they still expand our understanding of CPS for treating H. pylori infection.

Glucose-Responsive Nanochaperones Mediate Exendin-4 Delivery for Enhancing Therapeutic Effects.

Exendin-4 (Ex-4) is a promising therapeutic peptide for the clinical treatment of type 2 diabetes, but its instability and immunogenicity result in a short circulating half-life and low bioavailability, which severely limit its clinical application. Here, complex micelles with 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified and positively charged hydrophobic domains on the surface were devised as nanochaperones to mediate the delivery of Ex-4. The nanochaperones can bind Ex-4 on the surface via the synergy of electrostatic and hydrophobic interactions, leading to efficient loading and stabilization of Ex-4. More importantly, the immunogenic site of Ex-4 was shielded by the nanochaperones, thereby effectively reducing the immune clearance and prolonging the half-life. Hyperglycemia-triggered release of Ex-4 was achieved by the hydrophobic to the hydrophilic transformation of the FPBA-modified domains and the introduced negative charge because of the binding of glucose by FPBA. The Ex-4-loaded nanochaperones exhibited an enhanced therapeutic effect on type 2 diabetic mice.

Supratentorial hemangioblastoma at the anterior skull base: A case report.

BACKGROUND: Hemangioblastoma (HB) is a rare tumor, comprising about 2% of all intracranial tumors. Although it is a benign tumor, due to the abundant blood supply and its close relationship with adjacent cerebral blood vessels, surgical resection is difficult and may cause complications such as bleeding. If HB can be correctly diagnosed before surgery, complications can be avoided by methods such as vascular embolism before surgery. CASE SUMMARY: A 51-year-old male patient was admitted to our hospital because of blurred vision in his left eye for 2 years. Ophthalmological examination revealed oculus dexter vision acuity of 1.0 and oculus sinister vision acuity of 0.6. His left vision had tubular visual field, while his right vision had a partial defect. Computed tomography and magnetic resonance imaging showed a mass lesion at the left anterior base of the skull, which could have been a meningioma. During the operation, the tumor was found to be located at the entrance of the left optic nerve tube, closely adhering to the left optic nerve and the blood supply was extremely abundant. The tumor was carefully separated and diagnosed as HB postoperatively after pathological examination. CONCLUSION: A rare HB at the anterior skull base could be distinguished by its imaging features, which is essential to the surgical procedures.

Prophylactic central lymph node dissection performed selectively with cN0 papillary thyroid carcinoma according to a risk-scoring model.

Background: This study aimed to explore the risk factors of central lymph node metastasis (CLNM) in patients with clinical central lymph node-negative papillary thyroid carcinoma (PTC), and emphasize the guidance of the risk scoring model for prophylactic central lymph node dissection (pCLND) in patients with clinical lymph node-negative (cN0) PTC. Methods: A total of 582 patients with cN0 PTC who underwent unilateral/bilateral thyroidectomy and prophylactic central lymph node dissection (pCLND) in the Affiliated Hospital of Nantong University from January 2020 to February 2021 were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors of cN0 PTC. According to the independent risk factors of patients with cN0 PTC, a risk-scoring model was established. Then, the rationality of this risk scoring model was verified by additional clinical data of 112 patients with cN0 PTC in the Affiliated Hospital of Nantong University from March 2021 to April 2021. Results: Among 582 cases of cN0 PTC, 53.6% of the patients with cN0 had CLNM. The independent risk factors for CLNM in patients with cN0 PTC included male gender, <45 years of age, tumor with a maximum diameter of ≥1.0 cm, tumor location: middle/lower poles of the thyroid gland, multifocality, and extrathyroidal extension (ETE), and some ultrasound features, such as intra-nodular vascularity, microcalcification, irregular shape, and infiltrative margin. According to independent risk factors, a 24-point risk scoring model was established to predict CLNM in patients with cN0 PTC. Conclusions: Currently, prophylactic central neck lymph node dissection is a controversial operation, which should be selectively performed only for high-risk patients with cN0 PTC. For cN0 PTC patients with scores ≥14 and high-risk patients, even if no CLNM is found before surgery, routine prophylactic CLND is recommended. In addition, for cN0 PTC patients with a score of fewer than 14 points, it is recommended to perform fine-needle aspiration (FNA) before surgery, carefully assess the condition of the central lymph nodes, and then select the best surgical plan based on the results of the assessment.

Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2.

Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.

RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern.

The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam3CSK4-RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.

Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: adjusting macrophage polarization through the activin receptor-follistatin system.

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

Low expression of tRF-Pro-CGG predicts poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND & AIMS: tRFs (tRNA-derived RNA fragments) have been reported to facilitate cancer progression in multiple cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) remains to be determined. In this study, we mainly investigated the expression of tRF-Pro-CGG in pancreatic ductal adenocarcinoma and evaluated its relationship with the clinicopathology and survival time of patients. METHODS: 37 cases of pancreatic ductal adenocarcinoma, and 15 cases of normal pancreatic tissues were collected which were resected by surgery from January 2017 to June 2020 from the Department of Hepatobiliary and Pancreatic surgery of Changzhou second people's Hospital. The expression of tRF-Pro-CGG in paraffin-embedded tissues was detected by fluorescence in situ hybridization (FISH). The clinical data including age, sex, tumor location, tumor diameter, tumor clinical stage (TNM stage), depth of invasion, regional lymph node metastasis, serum CA199, and serum CEA were collected and analyzed retrospectively, whether the expression tRF-Pro-CGG was correlation with the pathological parameters and clinical outcomes of patients. RESULTS: The expression level of tRF-Pro-CGG was significantly downregulated in PDAC and associated with an advanced TNM stage (P=0.000) and the N stage (P=0.000) of patients. More importantly, low tRF-Pro-CGG expression predicted poor survival in PDAC patients (P=0.003). CONCLUSIONS: TRF-Pro-CGG is under-expressed in PDAC and is associated with short clinical survival and poor prognosis. tRF-Pro-CGG is an independent prognostic factor, which highlights its role as a potential biomarker for PDAC progression and therapy.

Synthesis and Evaluation of Liposomal Anti-GM3 Cancer Vaccine Candidates Covalently and Noncovalently Adjuvanted by αGalCer.

GM3, a typical tumor-associated carbohydrate antigen, is considered as an important target for cancer vaccine development, but its low immunogenicity limits its application. αGalCer, an iNKT cell agonist, has been employed as an adjuvant via a unique immune mode. Herein, we prepared and investigated two types of antitumor vaccine candidates: (a) self-adjuvanting vaccine GM3-αGalCer by conjugating GM3 with αGalCer and (b) noncovalent vaccine GM3-lipid/αGalCer, in which GM3 is linked with lipid anchor and coassembled with αGalCer. This demonstrated that ßGalCer is an exceptionally optimized lipid anchor, which enables the noncovalent vaccine candidate GM3-ßGalCer/αGalCer to evoke a comparable antibody level to GM3-αGalCer. However, the antibodies induced by GM3-αGalCer are better at recognition B16F10 cancer cells and more effectively activate the complement system. Our study highlights the importance of vaccine constructs utilizing covalent or noncovalent assembly between αGalCer with carbohydrate antigens and choosing an appropriate lipid anchor for use in noncovalent vaccine formulation.

The Gut Microbiota and Its Relevance to Peripheral Lymphocyte Subpopulations and Cytokines in Patients with Rheumatoid Arthritis.

Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut microbiome critically contribute to the development of rheumatoid arthritis (RA). Previous studies demonstrated the disturbance of lymphocyte subpopulations in RA patients. The purpose of this study was to explore the characteristics of gut microbiome and the associations between bacterium and lymphocyte subpopulations as well as cytokines in patients with RA. Fecal samples from 205 RA patients and 199 healthy controls (HCs) were collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The levels of peripheral lymphocyte subpopulation such as T, B, CD4+T, CD8+T, NK, T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs) of these subjects were detected by flow cytometry combined with standard absolute counting beads. The serum levels of cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17, tumour necrosis factor-α (TNF-α), and interferon-γ (INF-γ) were tested by flow cytometric bead array (CBA). Alpha and beta diversity of gut microbiome were explored by bioinformatics analysis. Spearman rank correlation test was used to explore the relationships between gut microbiome and lymphocyte subsets as well as serum cytokines. The diversity and relative abundance of intestinal microbiota in patients with RA were significantly different from those in HCs. Detailly, the abundant of phylum Proteobacteria in RA patients was more than that in HCs, while Firmicutes was less than in HCs. There was increased relative abundance of genus Clostridium_XlVa as well as genus Blautia, more abundance of Ruminococcus2 in patients with lower levels of T, B, CD4+T, and Tregs. In addition, the relative abundances of Pelagibacterium, Oxalobacter, ClostridiumXlVb, and ClostridiumXVIII were correlated with cytokines. Gut microbiome of RA patients was clearly different from that of HCs. Abnormal bacteria communities are associated with the altered levels of lymphocyte subpopulation and cytokines, which might be one of the pathogenesis of RA.

Associations among gonadal hormone, triglycerides and cognitive decline in female patients with major depressive disorders.

BACKGROUND: Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD). METHODS: The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020. RESULTS: In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients. CONCLUSIONS: Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline.