Polymeric nanomaterials encapsulating fluorescent polyindole-nido- carborane: design, synthesis and biological evaluation.

The water-soluble nido-carborane was prepared by alkali treatment of o-carborane. A polymer PInd containing a polyindole structure was synthesized and employed to label the modified o-carborane. Subsequently, four polymeric nanomaterials were synthesized with the objective of encapsulating them in order to enhance its bioavailability. The experimental results showed that the fluorescent complex encapsulated by the pH-sensitive polymer A had the best UV absorption and fluorescence intensity, and thus A-PInd-C was chosen for subsequent experiments. The Transmission electron microscopy images revealed that the compounds exhibited a rounded internal morphology, with the layers exhibiting a tightly stacked arrangement. The AFM imaging revealed that the surface of the sample exhibited a relatively uniform and smooth appearance. In vitro release experiments conducted under acidic conditions demonstrated that A-PInd-C was released in a predominantly linear manner, with a maximum release rate of 80% observed within 48 h. Cellular imaging experiments showed that the compound could enter HeLa and HCT-116 cells and was mainly distributed around the nucleus, especially in the acidic environment. The results of the cell proliferation toxicity experiments demonstrated that A-PInd-C exhibited inhibitory effects on HeLa, PC-3 and L02 cells. Among these, the inhibitory effect on PC-3 cells was the most pronounced, reaching up to 70%. In conclusion, this paper solves the problem of poor bioavailability of carborane by improving the boron containing compounds and also makes the system have potential for Boron neutron capture therapy.

Design, synthesis, and antitumor activity evaluation of BF3-o, m, p-phenylenediamine bridged with pyrimidine-indole BF3 adduction derivatives.

Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF3-o, m, p-phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF3. The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2 µg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug.

Research progress on Helicobacter pylori infection related neurological diseases.

Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.

Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment.

The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.

Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression.

Non-coding RNAs play important roles in tumor cells and macrophages and participate in their communication as messengers. Non-coding RNAs have an impact in tumor cell proliferation, migration, and apoptosis, and they also regulate the differentiation and regulation of immune cells. In macrophages, they stimulate the polarization of macrophages into M1 or M2 by regulating proteins related to signaling pathways; in tumor cells, non-coding RNAs can enter macrophages through exosomes and affect the latter polarization. The polarization of macrophages further regulates the biological functions of cancer cells. The direction of macrophage polarization determines tumor progression, angiogenesis and drug resistance. This often creates a feedback loop. Non-coding RNAs act as bridges between tumor cells and macrophages to regulate the balance of the tumor microenvironment. We reviewed the signaling pathways related to macrophage polarization and the regulatory mechanisms of non-coding RNA in tumor-associated macrophages M1 and M2, and discussed the potential applications and prospects of exosome engineering.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Tumor-derived CircRNA_102191 promotes gastric cancer and facilitates M2 macrophage polarization.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract and the fourth leading cause of death from cancer-related diseases. In recent years, many studies have found that circular RNAs play an important role in cancer. Tumor-associated macrophages (TAMs) are also critical for tumor progression. OBJECTIVE: This study examined the role of circRNA_102191 in gastric cancer progression. METHODS: The relative mRNA levels were determined by qRT-PCR. Western blotting and ELISA were used to detect the protein levels. In vitro proliferation was assessed using CCK8 and clonogenic assays. The migration and invasion of cell lines were assessed by transwell-based assays. The interactions between molecules were detected using a luciferase reporter assay. M0 macrophages were induced with PMA. M1 macrophages were induced with LPS and IFN-γ, and M2 macrophages were induced with IL-4. RESULTS: The expression of circRNA_102191 was enhanced significantly in gastric cancer cell lines and clinical tumor tissues. CircRNA_102191 promotes gastric cancer cell progression by regulating miR-493-3p and its downstream target gene XPR1. CircRNA_102191 can enhance the EMT process of gastric cancer cells by promoting the M2 polarization of macrophages. CONCLUSION: CircRNA_102191 promotes the biological function of gastric cancer cells by regulating the miR-493-3p/XPR1 axis and M2 macrophage polarization.

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.

BACKGROUND: Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. METHODS: The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. RESULTS: CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. CONCLUSIONS: Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

A novel long non-coding RNA XLOC_004787, is associated with migration and promotes cancer cell proliferation by downregulating mir-203a-3p in gastric cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms of cancer. However, the roles of most lncRNAs in the progression of gastric cancer (GC) remain largely unexplored. This study investigates the biological function and underlying mechanism of a novel lncRNA, XLOC_004787 in GC. METHODS: The location of XLOC_004787 in GES-1 cells and HGC-27 cells were detected by fluorescence in situ hybridization (FISH) assay. The expression levels of XLOC_004787 were assessed using quantitative real-time fluorescence PCR (qRT-PCR) in various cell lines, including GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, and HGC-27 cells. Functional assays such as Transwell migration, cell counting kit-8 (CCK-8), and colony formation experiments were employed to analyze the effects of XLOC_004787 and miR-203a-3p on cell migration and proliferation. Protein levels associated with GC in these cell lines were examined by Western blotting. The intracellular localization of ß-catenin and P-Smad2/3 was assessed using immunofluorescence (IF) assay. Additionally, the interaction between XLOC_004787 and miR-203a-3p was investigated using a dual luciferase assay. RESULTS: XLOC_004787 was localized at both the cytoplasm and nucleus of GES-1 cells and HGC-27 cells. Compared to normal tissues and GES-1 cells, XLOC_004787 expression was significantly upregulated in GC tissues and cells, with the highest and lowest expression observed in SGC-7901 and HGC-27 cells, respectively. Furthermore, a reduced expression of XLOC_004787 was seen to inhibit migration and proliferation in SGC-7901 cells. Western blotting analysis revealed that a decrease in XLOC_004787 expression correspondingly decreased the expression of N-cadherin, mmp2, mmp9, Snail, Vimentin, ß-catenin, C-myc, Cyclin D1, and TGF-ß, while concurrently increasing E-cadherin expression. This was also associated with diminished expression of P-Smad2/3 in relation to Smad2/3, and reduced P-Gsk3ß expression in comparison to Gsk3ß. Additionally, the nuclear entry of P-Smad2/3 and ß-catenin was reduced by lower XLOC_004787 expression. Amplifying XLOC_004787 expression via pcDNA_XLOC_004787 suggested a potential for cancer promotion. Notably, XLOC_004787 was found to negatively regulate mir-203a-3p expression, with potential binding sites identified between the two. Higher mir-203a-3p expression was observed to decrease migration and proliferation, and enhance E-cadherin expression. Conversely, suppression of mir-203a-3p expression suggested a potential promotion of proliferation and migration in GC cells. CONCLUSIONS: These results suggest that XLOC_004787, found to be upregulated in GC tissues, potentially promotes proliferation and migration in GC cells. This occurs through the activation of TGF-ß and Wnt/ß-catenin signaling pathways and the expression of EMT-related proteins. Additionally, XLOC_004787 may influence cell migration and proliferation by modulating the signaling pathway via the adsorption and inhibition of mir-203a-3p.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells.

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes' aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.

Application study of curcumin fluorescent complex coated with pharmaceutical excipients for cell imaging.

Taking curcumin as the starting point, ß-cyclodextrin was introduced on both sides, and lipid-soluble curcumin was coated by acrylic resin using oil-in-water strategy. Four different types of curcumin fluorescent complexes EPO-Curcumin (EPO-Cur), L100-55-Curcumin (L100-55-Cur), EPO -Curcumin-ß-cyclodextrin (EPO-Cur-ß-cd) and L100-55-Curcumin-ß-cyclodextrin (L100-55-Cur-ß-cd) were prepared to solve their own solubility and biocompatibility issues. The prepared curcumin fluorescent complexes were characterized and tested by spectroscopy. The characteristic peaks of 3446 cm-1 (hydroxyl group), 1735cm-1(carbonyl group) and 1455 cm-1 (aromatic group) were determined in the infrared spectrum. In the fluorescence emission spectrum, it was found that the emission intensity of different curcumin fluorescent complexes in polar solvents reached hundreds of times. Through the transmission electron microscopy shows that acrylic resin tightly coats curcumin into rods or clusters. In order to observe their compatibility with tumor cells more directly, live cell fluorescence imaging was carried out, and it was found that all four kinds of curcumin fluorescence complexes had good biocompatibility. In particular, the effect of EPO-Cur-ß-cd and L100-55-Cur-ß-cd is better than that of EPO-Cur and L100-55-Cur.

Effect of long non-coding RNA 114227 on gastric cancer cell proliferation and migration. / é•¿é“¾éžç¼–ç RNA 114227对胃癌细胞增殖与迁移能力的影响.

OBJECTIVES: Gastric cancer is a common cancer of the digestive system. Long non-coding RNA (lncRNA) plays an important role in the formation and development of gastric cancer. This study aims to investigate the effect of long non-coding lncRNA 114227 on biologic behaviors in gastric cancer cells. METHODS: The experiment was divided into 4 groups: a negative control (NC) group, a lncRNA 114227 small interference (si-lncRNA 114227) group, an empty vector (Vector) group, and an overexpression vector (OE-lncRNA 114227) group. The expressions of lncRNA 114227 in gastric mucosa and gastric cancer tissues, gastric mucosal epithelial cells and different gastric cancer strains were determined by real-time reverse transcription PCR (real-time RT-PCR).The proliferation were detected by CCK-8 assay in gastric cancer cells. The epithelial-mesenchymal transformation (EMT) was utilized by Transwell assay, scratch healing assay, and Western blotting in gastric cancer cells. The effect of lncRNA 114227 on proliferation of gastric cancer cells was detected by tumor bearing experiment in nude mice in vivo. RESULTS: The expression level of lncRNA 114227 in the gastric cancer tissues was significantly lower than that in the gastric mucosa tissues, and in 4 kinds of gastric cancer strains was all significantly lower than that in gastric mucosal epithelial cells (all P<0.01). In vitro, the proliferation and migration abilities of gastric cells were significantly reduced after overexpressing lncRNA 114227, and cell proliferation and migration were enhanced after silencing lncRNA 114227 (all P<0.05). The results of in vivo subcutaneous tumorigenesis in nude mice showed that the tumorigenic volume of the tumor-bearing mice in the OE-lncRNA 114227 group was significantly smaller than that of the Vector group, and the tumorigenic quality was lower than that of the Vector group (P<0.05), indicating that lncRNA 114227 inhibited tumorigenesis. CONCLUSIONS: The expression of lncRNA 114227 is downregulated in gastric cancer gastric cancer tissues and cell lines. LncRNA 114227 may inhibit the proliferation and migration of gastric cancer cells through EMT process.

CircDDX17 enhances coxsackievirus B3 replication through regulating miR-1248/NOTCH receptor 2 axis.

Coxsackievirus B3 (CVB3) was one of the most common pathogens to cause viral myocarditis. Circular RNAs as novel non-coding RNAs with a closed loop molecular structure have been confirmed to be involved in virus infectious diseases, but the function in CVB3 infection was not systematically studied. In this study, we identified that hsa_circ_0063331 (circDDX17) was drastically decreased after CVB3 infection by circRNA microarray. In vivo and in vitro, when cells or mice were infected with CVB3, the expression of circDDX17 was significantly reduced, as demonstrated by quantitative real-time PCR assays. Additionally, circDDX17 enhanced CVB3 replication by downregulating the expression of miR-1248 in HeLa and HL-1 cells, and miR-1248 regulated CVB3 replication through interacting with the gene coding for NOTCH Receptor 2 (NOTCH2), and NOTCH2 could upregulate methyltransferase-like protein 3 (METTL3). Taken together, this study suggested that circDDX17 promoted CVB3 replication and regulated NOTCH2 by targeting miR-1248 as a miRNAs sponge.

Circular RNA circPGD contributes to gastric cancer progression via the sponging miR-16-5p/ABL2 axis and encodes a novel PGD-219aa protein.

CircRNAs have critical effects on tumor development and progression. However, circPGD effect on gastric cancer (GC) is still elusive. Nuclear and cytoplasmic RNA fractionation, and RNA-FISH assay examined the localization of circPGD in MGC-803 cells. qRT-PCR was conducted to detect the expression and prognostic significance of circPGD, miR-16-5p, and ABL2 within GC tissues. Meanwhile, qRT-PCR, luciferase reporter assays, rescue, and western blotting assays confirmed the interactions between circPGD, miR-16-5p, and ABL2. Transwell, wound healing, and colony-formation assays, as well as CCK-8 and cell apoptosis assays, analyzed the functions of circPGD, miR-16-5p, ABL2, as well as PGD-219aa within GC cells. Western blotting and cell immunofluorescence experiments detected the differences in the expression of the related proteins. Finally, xenograft and metastatic mouse models were used to investigate circPGD function in vivo. Mass spectrometry was used to detect the existence of PGD-219aa in MGC-803 cells. CircPGD was localized in the cytoplasm and nucleus of MGC-803 cells. Compared with the control, circPGD and ABL2 expression increased within GC tissues and cells, and the miR-16-5p level was decreased. Functionally, circPGD promoted cell proliferation, migration and suppressed apoptosis in vitro. Mechanistically, circPGD sponged miR-16-5p for relieving miR-16-5p suppression on the corresponding target ABL2 via the SMAD2/3 and YAP signaling pathways. In addition, circPGD encodes a novel PGD-219aa protein that can enhance the growth and migration of GC cells, while inhibiting GC cells apoptosis via the SMAD2/3 and YAP signaling pathways. Furthermore, circPGD overexpression enhanced tumor aggressiveness, while circPGD knockdown inhibited tumor growth. Overall, circPGD has a novel oncogenic effect on GC cells, indicating the potential of circPGD as the tumorigenic factor and a promising diagnostic marker for GC.

High expression of ANRIL correlated with the poor prognosis in patients with cancer: A meta-analysis.

BACKGROUND: ANRIL, also called CDKN2B antisense RNA 1, is an important genetic susceptibility locus for cardiovascular diseases and associated with numerous pathologies, including several human cancers. OBJECTIVE: The relationship between ANRIL and the clinical outcome or prognosis of cancer patients was analyzed in this meta-analysis. METHODS: One thousand seven hundred eight cancer patients were selected in 23 studies from 3 databases (Pubmed, Cochrane Library, and EMBASE). RESULTS: A fixed-effects model indicated that the high expression of ANRIL is obviously linked to poor overall survival (OS) (Hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.57-2.00, P < .00001); the random-effects model revealed poor disease-free survival (DFS) (HR = 1.86, 95% CI: 1.46-2.37, P < .00001). A high level of ANRIL expression was also associated with the tumor size (small vs large, odds ratio [OR] = 0.57, 95% CI: 0.39-0.83, P = .003), TNM stage (I + II vs III + IV; OR = 0.40, 95% CI: 0.24-0.69, P = .0008), and lymph node metastasis (LNM) (Yes vs No, OR = 3.66, 95% CI: 1.46-9.17, P = .006). ANRIL was not related significantly to histologic differentiation compared to poor with moderate + well; the OR value is 0.74, 95% CI: 0.26-2.12, P = .58. In addition, evidence suggested that a high level of ANRIL was positively associated with human cancer type, follow-up time, and sample size. CONCLUSION: This meta-analysis demonstrated that ANRIL may be a valuable biomarker for predicting poor prognosis in cancer patients.

Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment.

Gastric cancer (GC) is a leading type of cancer. Although immunotherapy has yielded important recent progress in the treatment of GC, the prognosis remains poor due to drug resistance and frequent recurrence and metastasis. There are multiple known risk factors for GC, and infection with Helicobacter pylori is one of the most significant. The mechanisms underlying the associations of H. pylori and GC remain unclear, but it is well known that infection can alter the tumor microenvironment (TME). The TME and the tumor itself constitute a complete ecosystem, and the TME plays critical roles in tumor progression, metastasis, and drug resistance. H. pylori infection can act synergistically with the TME to cause DNA damage and abnormal expression of multiple genes and activation of signaling pathways. It also modulates the host immune system in ways that enhance the proliferation and metastasis of tumor cells, promote epithelial-mesenchymal transition, inhibit apoptosis, and provide energy support for tumor growth. This review elaborates myriad ways that H. pylori infections promote the occurrence and progression of GC by influencing the TME, providing new directions for immunotherapy treatments for this important disease. KEY POINTS: • H. pylori infections cause DNA damage and affect the repair of the TME to DNA damage. • H. pylori infections regulate oncogenes or activate the oncogenic signaling pathways. • H. pylori infections modulate the immune system within the TME.

Subacute thyroiditis complicated with multiple organ failure: A case report.

RATIONALE: Subacute thyroiditis is an inflammatory disease of the thyroid gland that is often caused by viral infections. Multiple organ failure (MOF) is mainly caused by acute inflammatory reactions resulting from severe infection or trauma. MOF due to subacute thyroiditis is extremely rare. PATIENT CONCERNS: A 48-year-old woman with a history of type 2 diabetes mellitus was admitted to our hospital because of subacute thyroiditis. However, the patient developed MOF during hospitalization. DIAGNOSIS: The patient was diagnosed with subacute thyroiditis complicated by MOF based on clinical symptoms and laboratory tests. INTERVENTIONS: The patient was initially admitted to the endocrinology ward for glucocorticoid and insulin therapies. When the condition deteriorated to MOF, the patient was transferred to the intensive care unit. Ventilator-assisted breathing, blood transfusion, albumin infusion, improved cardiac function, oral glucocorticoids, and insulin were administered to the patient. OUTCOMES: The patient was followed-up at 2-weeks intervals for over 2 months. Her thyroid function returned to normal and her blood sugar level was stable. Transaminase, serum creatinine, albumin, and myocardial enzyme levels were normal. LESSONS: MOF due to subacute thyroiditis is extremely rare. Especially in patients with elevated blood glucose or other immune dysfunctions, we should be alert to the occurrence of subacute thyroiditis with MOF.

Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials.

INTRODUCTION: Recent evidence suggested that vitamin D deficiency was associated with Hashimoto's thyroiditis (HT) pathogenesis and thyroid hypofunction. This study aimed to investigate whether vitamin D supplementation would be effective in the prevention and progression of hypothyroidism in patients with HT. METHODS: PubMed, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to August 2021. RESULTS: A total of 7 cohorts of patients from six clinical trials with 258 patients with HT were included. Significant difference was found (WMD = 19.00, 95% CI: 12.43, 25.58, p < 0.001; I2  = 90.0%, pheterogeneity  < 0.001) between the vitamin D group and control group in serum 25-hydroxyvitamin D level. And the combined results indicated vitamin D supplementation significantly reduced the level of thyroid peroxidase antibodies (TPO-Ab) compared to the control group (WMD = -158.18, 95% CI: -301.92, -14.45, p = 0.031; I2  = 68.8%, pheterogeneity  = 0.007). Whereas no significant differences were found on the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) compared to the control group (p > 0.05). WHAT IS NEW AND CONCLUSION: Our study demonstrated that vitamin D treatment might significantly increase the serum 25(OH)D levels and produce changes in TPO-Ab titres. No significant association was found between serum vitamin D treatment and the levels of TG-Ab, TSH, FT3 and FT4, suggesting that vitamin D is not associated with the function of the thyroid in patients with HT.