SZC010 suppresses breast cancer development by regulating the PI3K/Akt/NF-κB signaling pathway.

BACKGROUND: Breast cancer has become one of the leading causes of cancer deaths and is the most frequently diagnosed cancer among females worldwide. Despite advances in breast cancer therapy, metastatic disease in most patients will eventually progress due to the development of de novo or secondary resistance. Thus, it is extremely important to seek novel drugs with high effectiveness and low toxicity for systematic therapy. METHODS: We applied a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in this study to analyze and evaluate the cytotoxic activity of oleanolic acid (OA) and its derivatives in three types of breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-453). A flow cytometry assay was performed to access the mechanisms of apoptosis and cell cycle analysis in SZC010 in MDA-MB-453 cells. Apoptosis- and cyclin-related proteins were evaluated by western blot. The key proteins of the NF-κB and PI3K-Akt-mTOR signaling pathway were also evaluated by western blot. RESULTS: Our results revealed that all OA derivatives were more effective than OA in three types of breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-453). Among these seven OA derivatives, SZC010 exhibited the most potent cytotoxicity in MDA-MB-453 cells. Additionally, we observed that SZC010 treatment induced dose-and time-dependent growth inhibition in MDA-MB-453 cells. Furthermore, we demonstrated that SZC010 induced growth arrest in the G2/M phase and apoptosis by inhibition of NF-κB activation via the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Our data indicate that the novel OA derivative, SZC010, has great potential in breast cancer therapy.

Targeting thioredoxin reductase by eupalinilide B promotes apoptosis of colorectal cancer cells in vitro and in vivo.

Aberrant activation of thioredoxin reductase (TrxR) is correlated with tumor occurrence and progression, suggesting that TrxR inhibitors can be used as antitumor agents. In this study, we evaluated the anticancer efficacy of eupalinilides B on colorectal cancer cells. Eupalinilides B primarily targeted the conserved selenocysteine 498 residues in TrxR. Besides, it inhibited the enzyme activity in an irreversible manner. After eupalinilides B was used to pharmacologically inhibit TrxR, reactive oxygen species accumulated, and the intracellular redox balance was broken, finally causing oxidative stress-induced tumor cell apoptosis. Significantly, eupalinilides B treatment inhibited in vivo tumor growth. Targeting TrxR by eupalinilides B reveals the new mechanism underlying eupalinilides B and provides insight in developing eupalinilides B as the candidate antitumor chemotherapeutic agent for the treatment of cancer.

CMYC-initiated HNF1A-AS1 overexpression maintains the stemness of gastric cancer cells.

Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood. In this study, we investigated a lncRNA known as HNF1A-AS1, which is highly expressed in GCSC s and serves as a critical regulator of GCSC stemness and tumorigenesis. Our experiments, both in vitro and in vivo, demonstrated that HNF1A-AS1 maintained the stemness of GC cells. Further analysis revealed that HNF1A-AS1, transcriptionally activated by CMYC, functioned as a competing endogenous RNA by binding to miR-150-5p to upregulate ß-catenin expression. This in turn facilitated the entry of ß-catenin into the nucleus to activate the Wnt/ß-catenin pathway and promote CMYC expression, thereby forming a positive feedback loop that sustained the stemness of GCSCs. We also found that blocking the Wnt/ß-catenin pathway effectively inhibited the function of HNF1A-AS1, ultimately resulting in the inhibition of GCSC stemness. Taken together, our results demonstrated that HNF1A-AS1 is a regulator of the stemness of GCSCs and could serve as a potential marker for targeted GC therapy.

Case Report: A rare case of intramedullary spinal cord abscess with brain abscess caused by Klebsiella pneumoniae underwent surgical intervention.

Background: Intramedullary Spinal Cord Abscess (ISCA) is an uncommon infectious disease of the central nervous system. Since its first report in 1830, there have been very few documented cases associated with it. Here, we present a case of ISCA with cerebral abscess caused by Klebsiella pneumoniae. Case presentation: A 55-year-old male patient presented with head and neck pain, fever, and left limb weakness for 5 days. The diagnosis of ISCA with brain abscess caused by Klebsiella pneumoniae was confirmed through sputum culture, cerebrospinal fluid gene test, pus culture, and magnetic resonance imaging (MRI) as well as computerized tomography (CT) scan. The patient had a history of pulmonary tuberculosis and old tuberculous foci were observed in the lung. Initially considering tuberculosis as the cause due to unclear etiology at that time, anti-tuberculosis treatment was administered. However, due to rapid deterioration in the patient's condition and severe neurological dysfunction within a short period of time after admission, surgical intervention including incision and drainage for intramedullary abscess along with removal of brain abscess was performed. Subsequent postoperative follow-up showed improvement in both symptoms and imaging findings. Conclusion: Early diagnosis of central nervous system (CNS) abscess coupled with prompt surgical intervention and administration of appropriate antibiotics are crucial factors in preventing disease progression and reducing mortality rates.

Development and Validation of a Deep Learning Model to Reduce the Interference of Rectal Artifacts in MRI-based Prostate Cancer Diagnosis.

Purpose To develop an MRI-based model for clinically significant prostate cancer (csPCa) diagnosis that can resist rectal artifact interference. Materials and Methods This retrospective study included 2203 male patients with prostate lesions who underwent biparametric MRI and biopsy between January 2019 and June 2023. Targeted adversarial training with proprietary adversarial samples (TPAS) strategy was proposed to enhance model resistance against rectal artifacts. The automated csPCa diagnostic models trained with and without TPAS were compared using multicenter validation datasets. The impact of rectal artifacts on the diagnostic performance of each model at the patient and lesion levels was compared using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC). The AUC between models was compared using the DeLong test, and the AUPRC was compared using the bootstrap method. Results The TPAS model exhibited diagnostic performance improvements of 6% at the patient level (AUC: 0.87 vs 0.81, P < .001) and 7% at the lesion level (AUPRC: 0.84 vs 0.77, P = .007) compared with the control model. The TPAS model demonstrated less performance decline in the presence of rectal artifact-pattern adversarial noise than the control model (ΔAUC: -17% vs -19%, ΔAUPRC: -18% vs -21%). The TPAS model performed better than the control model in patients with moderate (AUC: 0.79 vs 0.73, AUPRC: 0.68 vs 0.61) and severe (AUC: 0.75 vs 0.57, AUPRC: 0.69 vs 0.59) artifacts. Conclusion This study demonstrates that the TPAS model can reduce rectal artifact interference in MRI-based csPCa diagnosis, thereby improving its performance in clinical applications. Keywords: MR-Diffusion-weighted Imaging, Urinary, Prostate, Comparative Studies, Diagnosis, Transfer Learning Clinical trial registration no. ChiCTR23000069832 Supplemental material is available for this article. Published under a CC BY 4.0 license.

MS3 Imaging Enables the Simultaneous Analysis of Phospholipid C═C and sn-Position Isomers in Tissues.

Mass spectrometry (MS) imaging of lipids in tissues with high structure specificity is challenging in the effective fragmentation of position-selective structures and the sensitive detection of multiple lipid isomers. Herein, we develop an MS3 imaging method for the simultaneous analysis of phospholipid C═C and sn-position isomers by on-tissue photochemical derivatization, nanospray desorption electrospray ionization (nano-DESI), and a dual-linear ion trap MS system. A novel laser-based sensing probe is developed for the real-time adjustment of the probe-to-surface distance for nano-DESI. This method is validated in mouse brain and kidney sections, showing its capability of sensitive resolving and imaging of the fatty acyl chain composition, the sn-position, and the C═C location of phospholipids in an MS3 scan. MS3 imaging of phospholipids has shown the capability of differentiation of cancerous, fibrosis, and adjacent normal regions in liver cancer tissues.

Corrigendum to: Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells.

A typographical error appeared in the author affiliation titled "Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells", published in Anti-Cancer Agents in Medicinal Chemistry, 2023, 23(15) [1]. Details of the error and a correction are provided here. Original: Author Affiliation: 2Department of Breast Medicine, Cancer Hospital Chinese Academy of Medical Science, Liaoning Provincial Cancer Hospital, Shenyang, Liaoning, 110042, China Corrected: Author Affiliation: 2Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China We regret the error and apologize to readers. The original article can be found online at https://www.eurekaselect.com/article/131718.

Relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and neutrophil gelatinase-associated lipocalin in early renal injury in H-type hypertension.

OBJECTIVE: To analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury. METHOD: A total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was < 10 µmol/L they were assigned to the non-H-type hypertensive group. Blood lipid indexes, renal function indexes and blood glucose indexes were collected, and the differences between the two groups were compared. Furthermore, MTHFR C677T genotype distribution and allele frequency and Hcy level of MTHFR C677T genotype were compared, and logistic multiple regression analysis was conducted for the correlation of different genotypes of MTHFR C677T and the early kidney injury marker NGAL. RESULTS: In the non-H-type hypertensive group, the levels of Hcy and NGAL, cystatin, blood urea nitrogen, serum creatinine, uric acid, serum ß2-microglobulin and urinary microalbumin-to-creatinine ratio increased significantly, and the glomerular filtration rate level decreased significantly, when compared with the H-type hypertensive group, with statistical differences (p < 0.05). The H-type hypertensive group and the non-H-type hypertensive group had significant differences in the CC, CT and TT genotypes and allele frequencies at the MTHFR C677T locus. The MTHFR C677T gene mutation rate of the H-type hypertensive group was significantly higher than that of the non-H-type hypertensive group. The H-type hypertensive group had higher levels of the TT genotype and CT genotype Hcy. There was a statistical difference (p < 0.05). CONCLUSION: Methylenetetrahydrofolate reductase C677T polymorphism is correlated with the Hcy level, and its gene polymorphism will affect the Hcy level. Methylenetetrahydrofolate reductase C677T polymorphism has an interactive effect with NGAL. Screening NGAL and reducing Hcy levels are valuable methods for the prevention and treatment of early renal injury in patients with H-type hypertension and help improve the prognosis of patients and their quality of life.

LncRNA LY6E-DT and its encoded metastatic-related protein play oncogenic roles via different pathways and promote breast cancer progression.

Abnormal long noncoding RNA (lncRNA) expression plays an important role in tumor invasion and metastasis. Here, we show that lncRNA LY6E divergent transcript (LY6E-DT) levels are increased in breast cancer (BC) tissues. Transcription factor SP3 binds directly to the LY6E-DT promoter, activating its transcription. Moreover, LY6E-DT N6-methyladenosine modification by methyltransferase-like protein 14 (METTL14) promotes its expression, dependent on the "reader" insulin-like growth factor 2 mRNA binding protein 1(IGF2BP1)-dependent pathway. Notably, we discovered that the lncRNA LY6E-DT encodes a conserved 153-aa protein, "Metastatic-Related Protein" (MRP). Both LY6E-DT and MRP promote BC invasion and metastasis, and MRP expression could distinguish BC patients with lymph node metastasis from those without. Mechanistically, MRP binds heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC), enhancing the interaction between HNRNPC and epidermal growth factor receptor (EGFR) mRNA, increasing EGFR mRNA stability and protein expression and subsequently activating the phosphatidylinositol 3­kinase/protein kinase B signaling (PI3K) pathway. LncRNA LY6E-DT promotes the interaction between Y box binding protein 1 (YBX1) and importin α1 and increases YBX1 protein entry into the nucleus, where it transcriptionally activates zinc finger E-box-binding homeobox 1(ZEB1). Our findings uncover a novel regulatory mechanism underlying BC invasion orchestrated by LY6E-DT and its encoded MRP.

Mobility-Modulated Sequential Dissociation Analysis Enables Structural Lipidomics in Mass Spectrometry Imaging.

Spatial lipidomics based on mass spectrometry imaging (MSI) is a powerful tool for fundamental biology studies and biomarker discovery. But the structure-resolving capability of MSI is limited because of the lack of multiplexed tandem mass spectrometry (MS/MS) method, primarily due to the small sample amount available from each pixel and the poor ion usage in MS/MS analysis. Here, we report a mobility-modulated sequential dissociation (MMSD) strategy for multiplex MS/MS imaging of distinct lipids from biological tissues. With ion mobility-enabled data-independent acquisition and automated spectrum deconvolution, MS/MS spectra of a large number of lipid species from each tissue pixel are acquired, at no expense of imaging speed. MMSD imaging is highlighted by MS/MS imaging of 24 structurally distinct lipids in the mouse brain and the revealing of the correlation of a structurally distinct phosphatidylethanolamine isomer (PE 18 : 1_18 : 1) from a human hepatocellular carcinoma (HCC) tissue. Mapping of structurally distinct lipid isomers is now enabled and spatial lipidomics becomes feasible for MSI.

CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages.

The metastasis of cancer cells is the main cause of death in patients with gastric cancer (GC). Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5 to WD7 domains of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ERK signaling pathway, which resulted in IL-4 and IL-10 secretion. Polarized M2 macrophages induced premetastatic niche formation and promoted GC metastasis by secreting TGFB1, which created a TGFB1/JUN/CAP2 positive-feedback loop to activate CAP2 expression continuously. Furthermore, we identified salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion capabilities by suppressing the SRC/FAK/ERK signaling pathway. Our data suggest that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis in GC.

ETS-1-activated LINC01016 over-expression promotes tumor progression via suppression of RFFL-mediated DHX9 ubiquitination degradation in breast cancers.

Long non-coding RNAs (lncRNAs) are key regulators during the development of breast cancer (BC) and thus may be viable treatment targets. In this study, we found that the expression of the long intergenic non-coding RNA 01016 (LINC01016) was significantly higher in BC tissue samples with positive lymph node metastasis. LINC01016, which is activated by the transcription factor ETS-1, contributes to the overt promotion of cell proliferation activity, enhanced cell migratory ability, S phase cell cycle arrest, and decreased apoptosis rate. By RNA pull-down assays and mass spectrometry analyses, we determined that LINC01016 competitively bound and stabilized DHX9 protein by preventing the E3 ubiquitin ligase RFFL from binding to DHX9, thereby inhibiting DHX9 proteasomal degradation. This ultimately led to an increase in intracellular DHX9 expression and activated PI3K/AKT signaling, with p-AKT, Bcl-2, and MMP-9 involvement. This is the first study to reveal that the LINC01016/DHX9/PI3K/AKT axis plays a critical role in the progression of BC, and thus, LINC01016 may serve as a potential therapeutic target for patients with BC.

Investigation of the Apoptosis Inducing and ß-catenin Silencing by Tetradentate Schiff Base Zinc(II) Complex on the T-47D Breast Cancer Cells.

INTRODUCTION: Several mechanisms are known for the anticancer effects of cisplatin. However, its most wellknown function involves binding to DNA and activating the DNA damage response. METHODS: Despite its good effects, the treatment process often leads to chemoresistance and affects the mechanisms that support cell survival, such as pathways that promote cell growth, apoptosis, DNA damage repair, and endocytosis. For this reason, we investigated the effects of a new metal complex (tetradentate Schiff base zinc(II) complex) on breast cancer cells (T-47D). We evaluated its effect on cytotoxicity, apoptosis, and drug resistance in comparison to cisplatin. RESULTS: The results of the MTT test showed that tetradentate Schiff base zinc(II) complex has good cytotoxicity compared to cisplatin. The IC50 values for the [Zn(SB)]Cl2 complex and cisplatin after 72 h of exposure were equal to 42.1 and 276.1 µM, respectively. Real-time PCR assay confirmed that the [Zn(SB)]Cl2 complex activated the mitochondrial pathway of apoptosis and increased the expression of Bak1 and caspase-3 genes significantly compared to cisplatin. More importantly, the [Zn(SB)]Cl2 was able to reduce the expression of the ß-catenin gene, which plays a role in drug resistance, by 0.011 compared to the control. CONCLUSION: Therefore, we can hope for this new complex because, without the help of any ß-catenin silencing agent, it was able to inhibit the drug resistance in the T-47D cell line that overexpresses the ß-catenin gene.

Glutamine inhibits inflammation, oxidative stress, and apoptosis and ameliorates hyperoxic lung injury.

Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln's effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln's function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway.

LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor that threatens women's health. Attention has been paid on the study of long- non-coding RNA (lncRNA) in breast cancer. However, the specific mechanism remains not clear. METHODS: In this study, we explored the role of lncRNA BC069792 in breast cancer. In vitro and in vivo functional experiments were carried out in cell culture and mouse models. High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were used to evaluate differentially expressed genes and mRNA expression, Western blot and immunohistochemical staining were used to detect protein expression. RNA immunoprecipitation assay and dual-luciferase activity assay were used to evaluate the competing endogenous RNAs (ceRNA), and rescue and mutation experiments were used for verification. RESULTS: We found that lncRNA BC069792 was expressed at a low level in breast cancer tissues, and significantly decreased in breast cancer with high pathological grade, lymph node metastasis and high Ki-67 index groups. Moreover, BC069792 inhibited the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Mechanically, BC069792 acts as a molecular sponge to adsorb hsa-miR-658 and hsa-miR-4739, to up-regulate the protein expression of Potassium Voltage-Gated Channel Q4 (KCNQ4), inhibits the activities of JAK2 and p-AKT, and plays a role in inhibiting breast cancer growth. CONCLUSIONS: LncRNA BC069792 plays the role of tumor suppressor gene in breast cancer and is a new diagnostic index and therapeutic target in breast cancer.

Hypoglycemic medicines in the treatment of Alzheimer's disease: Pathophysiological links between AD and glucose metabolism.

Alzheimer's Disease (AD) is a global chronic disease in adults with beta-amyloid (Aß) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3ß and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.

Advances in the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease that affects approximately one-quarter of the global adult population, posing a significant threat to human health with wide-ranging social and economic implications. The main characteristic of NAFLD is considered that the excessive fat is accumulated and deposited in hepatocytes without excess alcohol intake or some other pathological causes. NAFLD is a progressive disease, ranging from steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Therefore, NAFLD will probably emerge as the leading cause of end-stage liver disease in the coming decades. Unlike other highly prevalent diseases, NAFLD has received little attention from the global public health community. Liver biopsy is currently considered the gold standard for the diagnosis and staging of NAFLD because of the absence of noninvasive and specific biomarkers. Due to the complex pathophysiological mechanisms of NAFLD and the heterogeneity of the disease phenotype, no specific pharmacological therapies have been approved for NAFLD at present, although several drugs are in advanced stages of development. This review summarizes the current evidence on the pathogenesis, diagnosis and treatment of NAFLD.

Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China.

BACKGROUND: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020-2022. METHOD: We collected HIV incidence and mortality data from the website of the National Health Commission of the People's Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020-2022 with those in 2015-2019 using a two-ratio Z-test. RESULTS: From January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015-2019 (pre-COVID-19 stage) and 2020-2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p <  0.001) in 2020-2022 compared with that in 2015-2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p <  0.001), in 2020-2022 compared with those in 2015-2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015-2019, while the incidence during the routine stage in May 2020-December 2022 increased by 27.4334%, (all p <  0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p <  0.001). CONCLUSIONS: The findings suggest that China's dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without China's dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020-2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.

HRCT1, negatively regulated by miR-124-3p, promotes tumor metastasis and the growth of gastric cancer by activating the ERBB2-MAPK pathway.

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer. METHODS: Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1. RESULTS: HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p. CONCLUSIONS: The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer.