Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

Isolation, genome analysis and comparison of a novel parainfluenza virus 5 from a Siberian tiger (Panthera tigris).

Paramyxoviruses are important pathogens affecting various animals, including mammals and humans. Parainfluenza virus 5 (PIV5)-a member of the family Paramyxoviridae-is a major threat to the health of mammals and humans. However, studies on terrestrial wild animals infected with PIV5 are scanty. In this study, we utilized reverse transcription PCR to detect PIV5 infection in the visceral organ tissues of a Siberian tiger (Panthera tigris ssp. altaica) with vomiting, diarrhea, and dyspnea before its death. A novel PIV5 (named SR strain) with a slowly progressive cytopathic effect was isolated in Vero cells and validated using a transmission electron microscope. Full-length sequencing and analysis revealed that the whole genome of the PIV5 SR strain contained 15,246 nucleotides (nt) and seven non-overlapping genes (3'-N-V/P-M-F-SH-HN-L-5') encoding eight proteins. Phylogenetic analysis of three PIV5 strains identified in the same zoo confirmed that PIV5 strains SR and ZJQ-221 shared the closest genetic relationship as they were clustered in the same branch, while the recently found Siberian tiger strain SZ2 kept a certain distance and formed a relatively unique branch. Furthermore, mutations of nt and amino acids (aa) between strains ZJQ-221, SR, and SZ2 were identified. In summary, we report the identification and genomic characterization of a novel PIV5 strain SR isolated in a Siberian tiger, which may help future research on interspecific transmission mechanisms.

Mo-doping and construction of the heterostructure between NiFe LDH and NiSx co-trigger the activity enhancement for overall water splitting.

To reduce the preparation cost of high-purity hydrogen, it is necessary to search suitable non-precious metal catalysts with high activity and robust stability. Herein, two means (heteroatom-doping and the heterostructure construction) were adopted together to improve the dual-function activity of NiFe LDH which was widely used in water electrolysis. Mo doped NiFe LDH nanoflowers were firstly generated by hydrothermal reaction, and then NiSx was modified on the petals via electrodeposition. Finally, the obtained NF/Mo-NiFe LDH/NiSx with large electrochemical active area exhibits the expected electrochemical performance with the overpotential at 100 mA cm-2 of 169 and 249 mV for hydrogen evolution (HER) and oxygen evolution reaction (OER) respectively. Assembling NF/Mo-NiFe LDH/NiSx into a two-electrode device for the integral water electrolysis, it just requires a cell voltage of 1.69 V to drive a current density of 100 mA cm-2, and keeps stable after 50-hour continuous operation in 1.0 M KOH. Mo-doping not only regulates the electronic structure of the transition metals and reduces the energy barrier of HER intermediates, but also facilitates the generation of reactive sites for OER. Meanwhile, the construction of heterointerface ensures the synergism between NiSx and Mo-NiFe LDH and accelerates the electron transfer across interfaces, thus enhancing the bifunctional performance.

Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.

OBJECTIVE: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. METHODS: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. RESULTS: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. CONCLUSION: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy.

Emerging role of RNA modification and long noncoding RNA interaction in cancer.

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

Preharvest application of MeJA enhancing the quality of postharvest grape berries via regulating terpenes biosynthesis and phenylpropanoid metabolisms.

Methyl jasmonate (MeJA) is an important phytohormone that regulates the development of grape, but the effect and underpin mechanism of its preharvest application on secondary metabolites accumulation in postharvest grape berries are still unclear. In this study, the transcriptome profiles combined with metabolic components analysis were used to determine the effect of preharvest MeJA application on the quality formation of postharvest rose-flavor table grape Shine Muscat. The results indicated that preharvest MeJA treatment had no significant effect on TSS content, but had a down-regulation effect on the accumulation of reducing sugar and titratable acid in the berries. The content of chlorophylls and carotenoids in treated berries was significantly higher than that of the control. Many phenolic components, such as trans-ferulic acid, resveratrol, quercetin, and kaempferol, were sensitive to MeJA and their contents were also significantly higher than that of the control under MeJA treatments during the shelf life. Compared with other volatile aroma components, terpenoid components were more sensitive to preharvest MeJA signals, the content of which presented an overall upward trend with increasing MeJA concentration and prolonging storage time. Furthermore, most of the differentially expressed genes in the general phenylpropanoid pathway and terpenoid biosynthesis pathway were up-regulated responding to MeJA signals. The most upregulated regulatory factors, such as VvWRKY72, VvMYB24, and VvWRI1, may be involved in MeJA signal transduction and regulation. Preharvest MeJA may be an effective technique for enhancing the quality of postharvest Shine Muscat grape berries, with its positive effect on enhancing the characteristic aroma and nutritional components.

Effect of Supplementary Light with Different Wavelengths on Anthocyanin Composition, Sugar Accumulation and Volatile Compound Profiles of Grapes.

Protected cultivation is currently one of the main cultivation modes for grape production, but the long-term use of plastic film will have a certain negative impact on the light environment in vineyards, which in turn causes poor colouring, low sugar content and a lack of aroma in some red grape varieties. Supplementing light can be an effective way to mitigate these problems. In this study, vines of three red table grape varieties ('Summer Black', 'Xinyu' and 'Queen Nina') cultivated in a plastic greenhouse were supplemented with red, blue, white and red-blue light from veraison to harvest. All four supplemental light treatments increased the content of anthocyanins, sugars and volatile compounds in three grape varieties compared to CK (no supplemental lighting). Red-blue light treatment was the most favourable for the accumulation of anthocyanins and sugars, and the grapes treated with blue light had the highest content of volatile compounds. The grapes treated with red-blue light all obtained the highest composite scores via principal component analysis. For most of the sensory properties, the highest scores were obtained by the red-blue light-treated grapes. The results of this study will be useful in improving the colouring, sugar, and aroma content of grapes under protected cultivation.

Dysregulation of immunity by cigarette smoking promotes inflammation and cancer: A review.

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.

LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway.

OBJECTIVE: Emerging evidence indicates that long non-coding RNA (lncRNA) RP11-93B14.5 facilitates tumor progression in variety of malignancies. The present study proposed to study the functional effect of lncRNA RP11-93B14.5 in gastric cancer (GC) as well as the underlying mechanism. METHODS: Bioinformatics analysis was utilized to analyze lncRNA expression in GC tissues. siRNA was used for knockdown of RP11-93B14.5 in GC cells MKN45 and KATO III. The stable knockdown cell lines were constructed by CRISPR-Cas9. Cell counting kit-8 (CCK-8) assay and soft agar colony formation assay were used to analyze GC cell viability. Flow cytometry analysis was performed to analyze the cell cycle distribution of MKN45 and KATO III. RNA sequencing (RNA-seq) was employed to detect differential genes after transfection with siRP11-93B14.5. Quantitative PCR (Q-PCR) was used to examine gene expression in GC cell lines. Western-blot assay was used to measure protein levels. RNA fluorescent in situ hybridization (FISH) was conducted for lncRNA cellular location and expression. RESULTS: Based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, RP11-93B14.5 was upregulated in GC tissue, which was also verified in GC cell lines in comparison to the normal gastric epithelial HFE145 cells. Knockdown of RP11-93B14.5 decreased cell viability and the colony number of MKN45 and KATO III cells, and altered cell cycle distribution in vitro. RNA-seq analysis revealed RP11-93B14.5 may modulate genes expression of S100A2 and TIMP2 in MKN45 and KATO III cells. Mechanistically, RP11-93B14.5 may drive the progression of GC via S100A2 related-PI3K/AKT signaling pathway. CONCLUSIONS: LncRNA RP11-93B14.5 knockdown alleviated the malignant phenotypes of GC cells through regulating PI3K/AKT. Our results provide evidence for the role of lncRNAs in regulating tumor progression.

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?

Reactive oxygen species (ROS) are a class of highly reactive oxidizing molecules, including superoxide anion (O2•-) and hydrogen peroxide (H2O2), among others. Moderate levels of ROS play a crucial role in regulating cellular signaling and maintaining cellular functions. However, abnormal ROS levels or persistent oxidative stress can lead to changes in the tumor microenvironment (TME) that favor cancer development. This review provides an overview of ROS generation, structure, and properties, as well as their effects on various components of the TME. Contrary to previous studies, our findings reveal a dual effect of ROS on different components of the TME, whereby ROS can either enhance or inhibit certain factors, ultimately leading to the promotion or suppression of the TME. For example, H2O2 has dual effects on immune cells and non-cellular components within the TME, while O2•- has dual effects on T cells and fibroblasts. Furthermore, each component demonstrates distinct mechanisms of action and ranges of influence. In the final section of the article, we summarize the current clinical applications of ROS in cancer treatment and identify certain limitations associated with existing therapeutic approaches. Therefore, this review aims to provide a comprehensive understanding of ROS, highlighting their dual effects on different components of the TME, and exploring the potential clinical applications that may pave the way for future treatment and prevention strategies.

Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Starch from Pueraria lobata and the amylose fraction alleviates dextran sodium sulfate induced colitis in mice.

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 µm. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 °C, with a high range of gelatinization (15.15 °C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-κB/IL-1ß axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.

Patterns and predictors of adolescent life change during the COVID-19 pandemic: a person-centered approach.

The present study investigated patterns of adolescent life changes across multiple life domains and utilized a holistic-interactionistic perspective to examine their individual, familial, and societal correlates with a sample of 2544 Chinese parent-adolescent dyads. Adolescents were aged from 10 to 19 years old (50.16% girls). Latent profile analysis revealed five life change profiles, including three improved profiles at various degrees, one unchanged profile, and one worsened profile. The majority of adolescents had an improved or unchanged life. Multinomial logistic regression analyses found that most of the individual, familial, and societal factors predicted the group memberships. Notably, parent-adolescent conflict was a significant factor that predicted memberships of all patterns. These findings show the resilience of adolescents and indicate the need for policies and interventions that consider the holistic nature of adolescents' person-context system, especially during a global crisis such as the COVID-19 pandemic.

Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review.

Hypoxia-inducible factors (HIFs), central regulators for cells to adapt to low cellular oxygen levels, are often overexpressed and activated in breast cancer. HIFs modulate the primary transcriptional response of downstream pathways and target genes in response to hypoxia, including glycolysis, angiogenesis and metastasis. They can promote the development of breast cancer and are associated with poor prognosis of breast cancer patients by regulating cancer processes closely related to tumor invasion, metastasis and drug resistance. Thus, specific targeting of HIFs may improve the efficiency of cancer therapy. In this review, we summarize the advances in HIF-related molecular mechanisms and clinical and preclinical studies of drugs targeting HIFs in breast cancer. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for HIF targeting are increasingly being developed. Therefore, we highlight the HIF related DDS, including liposomes, polymers, metal-based or carbon-based nanoparticles.

PROTACs in gastrointestinal cancers.

Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.

Therapeutic prospects of ceRNAs in COVID-19.

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus; however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.

Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma.

Background: Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear. Methods: Data were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat. Results: The expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells. Conclusions: Dysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.

Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges.

Over the past decade, immunotherapy, especially cell-based immunotherapy, has provided new strategies for cancer therapy. Recent clinical studies demonstrated that adopting cell transfer of tumor-infiltrating lymphocytes (TILs) for advanced solid tumors showed good efficacy. TIL therapy is a type of cell-based immunotherapy using the patient's own immune cells from the microenvironment of the solid tumor to kill tumor cells. In this review, we provide a comprehensive summary of the current strategies and challenges in TIL isolation and generation. Moreover, the current clinical experience of TIL therapy is summarized and discussed, with an emphasis on lymphodepletion regimen, the use of interleukin-2, and related toxicity. Furthermore, we highlight the clinical trials where TIL therapy is used independently and in combination with other types of therapy for solid cancers. Finally, the limitations, future potential, and directions of TIL therapy for solid tumor treatment are also discussed.