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Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

AbstractThe chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

ObjectThere is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms.MethodsGSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions.ResultsBetween the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software’s MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p.ConclusionOur research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.

Abstract Background Methamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified. Methods We examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape ( www.metascape.org ). Results The viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process. Conclusions The results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells.

Gastrointestinal probiotics play an important role in maintaining intestinal bacteria homeostasis. They might benefit people with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which remains a global health challenge. However, there is a controversy regarding the efficacy of probiotics for the treatment of AIDS. This study systematically reviewed the evidence of the effects of existing probiotic interventions on AIDS and sought to provide information on the role of probiotics in the treatment of HIV/AIDS patients. A meta-analysis of studies identified by screening multiple databases was performed using a fixed-effects model in Review Manager 5.2 software. The meta-analysis showed that probiotics could reduce the incidence of AIDS-related diarrhea (RR = 0.60 (95% CI: 0.44–0.82), p = 0.001). The short-term use of probiotics (supplementation duration shorter than 30 days) did not reduce the incidence of diarrhea (RR = 0.76 (95% CI: 0.51–1.14), p = 0.19), while the long-term use of probiotics (supplementation duration longer than 30 days) reduced diarrhea (RR = 0.47 (95% CI: 0.29–0.76), p = 0.002). Probiotics had no effect on CD4 cell counts in HIV/AIDS patients (MD = 21.24 (95% CI: −12.95–55.39), p = 0.22). Our data support that probiotics were associated with an obvious reduction in AIDS-related diarrhea, which indicates the need for additional research on this potential preventive strategy for AIDS.

Abstract Objective This study aims to establish EQ-5D-Y-3L population norms in Jiangsu, China by conducting a large-scale cross-sectional survey. Methods Children and adolescents aged 9–17 from three cities of Jiangsu Province were selected by multistage stratified random sampling to complete the EQ-5D-Y-3L instrument independently. Population norms for Jiangsu, China were determined by calculating statistics based on age and gender. Logistic and Tobit regression models were employed to explain the relationship between HRQoL and factors such as sociodemographic characteristics/recent acute symptoms (experienced fever/cough/sore throat/diarrhea in the past two weeks). Results Three cities yielded 37,574 valid samples (a sample validity rate of 95.4%). The EQ-5D-Y-3L utility values (mean ± SD) were 0.964 ± 0.085 for males and 0.958 ± 0.077 for females. Males scored 85.94 ± 19.62 and females scored 84.83 ± 18.45 on the VAS (mean ± SD), while the percentages of respondents reporting full health ranged from 58.3 to 78.8%. The dimension in which most respondents reported having no problems was “feeling worried, sad, or unhappy” (23.0%). And the lowest HRQoL was shown in the 14-year-old age group. Gender, age, board at school, and BMI were found to have an association with HRQoL. In addition, recent acute symptoms also correlate with some aspects of HRQoL. Conclusions This study established EQ-5D-Y-3L population norms in Jiangsu, China for the first time. These norms will support resource allocation decision-making and be used as a reference for health evaluation studies.

Intratumor heterogeneity (ITH) leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC) genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X), SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

The title compound, C20H19NO, is a substructure of CP-640186, a potent inhibitor of mammalian acetyl-coenzyme A carboxylases. In the crystal structure, the amide group forms a dihedral angle of 87.0 (1)° with the plane of the anthracene unit and the piperidine ring adopts a chair conformation. Molecules are arranged into layers parallel to (100) and adjacent anthracene units within layers form dihedral angles of 13.2 (1)°. C—H...O interactions from the piperidine rings to the C=O group of the amide are observed between layers.

Abstract The combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that ∆9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.

A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in CD86+ cells in the injury site with MSC-NHC was mainly attributed to NHC. One and eight weeks after injury, we found a greater CD206+/CD86+ cell ratio with MSC-NHC or NHC, but not MSC-PBS, indicating a shift from a pro-inflammatory towards an anti-inflammatory milieu in the injury site. Eight weeks after injury, the injury size was significantly reduced with MSC-NHC, NHC, and MSC-PBS. At this time, astrocyte, and axon presence in the injury site was greater with MSC-NHC compared with MSC-PBS. We did not find a significant effect of NHC on MSC transplant survival, and hind limb function was similar across all groups. However, we did find fewer macrophages at 1 week post-injury, more macrophages polarized towards a pro-regenerative phenotype at 1 and 8 weeks after injury, and reduced injury volume, more astrocytes, and more axons at 8 weeks after injury in rats with MSC-NHC and NHC alone compared with MSC-PBS; these findings were especially significant between rats with MSC-NHC and MSC-PBS. The data support further study in the use of an NHC-MSC combination transplant in the contused spinal cord.

Background: With the continuous large-scale development of the COVID-19 vaccine, the acceptance of vaccination and its influencing factors at the individual level have become crucial to stemming the pandemic. This study aims to explore the factors that influence the acceptance of the COVID-19 vaccine among international college students. Methods: The target population constituted international students pursuing various degrees in Jiangsu Province through an online cross-sectional study. A cluster random sampling was performed using a self-administered questionnaire. The Health Belief Model and Knowledge, Attitude/Beliefs, and Practice Theory served as the underlying theories to understanding the factors that influence vaccine acceptance. Results: We received 330 responses. About 36.4% intended to accept the vaccine. The acceptance varied across respondents’ place of residence, program of study, continent of origin, knowledge, susceptibility, severity, benefits, and cues to action (p < 0.05). A multivariable logistics regression revealed cues to action (p < 0.001), the perception of COVID-19 vaccination benefits (p = 0.002), and the perception of barriers (p < 0.001) that were associated with vaccine acceptance. Conclusions: The acceptance of the COVID-19 vaccine was low among international students. The correct and comprehensive beliefs of the target groups regarding the benefits and barriers of the vaccination must be raised. Various effective social strategies must be adopted to trigger the intention of COVID-19 vaccination. The study findings will inform the decisions of public health campaigners, aimed at reducing vaccine hesitation when the COVID-19 vaccine is widely available.