Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Phytochemical and pharmacological properties of the genus Tamarix: a comprehensive review.

The genus Tamarix in the Tamaricaceae family consists of more than 100 species of halophyte plants worldwide that are mainly used to improve saline-alkali land and for coastal windbreaks, sand fixation, and afforestation in arid areas. A considerable number of species in this genus are also used as traditional medicines to treat various human diseases, especially in Asian and African countries. This review presents a comprehensive summary of 655 naturally occurring compounds derived from the genus Tamarix, categorized into flavonoids (18.0%), phenols (13.9%), tannins (9.3%), terpenoids (10.5%), essential oils (31.0%), and others (17.3%). The investigation revealed that the crude extracts and phytochemicals of this genus exhibited significant therapeutic potential, including anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, antibacterial, and antifungal activities. Six species of Tamarix have anticancer effects by causing cancer cell death, inducing autophagy, and stopping cell division. Seven species from the same genus have the potential for treating diabetes by inhibiting α-glycosidase activity, suppressing human islet amyloid polypeptide, regulating blood glucose levels, and modulating autophagy or inflammation. The focus on antibacterial and antidiabetic effects is due to the presence of volatile oil and flavonoid components. Extensive research has been conducted on the biological activity of 30 constituents, including 15 flavonoids, 5 phenols, 3 terpenoids, 1 tannin, and 6 others. Therefore, future research should thoroughly study the mechanisms of action of these and similar compounds. This is the most comprehensive review of the phytochemistry and pharmacological properties of Tamarix species, with a critical assessment of the current state of knowledge.

Spatio-temporal expression patterns of glycine-rich beta proteins and cysteine-rich beta proteins in setae development of Gekko japonicus.

BACKGROUND: Setae on the pad lamellae of the Japanese gecko Gekko japonicus (Schlegel, 1836), a vital epidermal derivative, are primarily composed of cornified beta-proteins (CBPs) and play a pivotal role in adhesion and climbing. The amino acid composition of CBPs might be a determining factor influencing their functional properties. However, the molecular mechanisms governed by CBP genes with diverse amino acid compositions in setae development remain unexplored. RESULTS: Based on RNA-seq analyses, this study confirmed that all G. japonicus CBPs (GjCBPs) are involved in setae formation. Cysteine-rich CBPs encoding genes (ge-cprp-17 to ge-cprp-26) and glycine-rich CBPs encoding genes (ge-gprp-17 to ge-gprp-22) were haphazardly selected, with quantitative real-time PCR revealing their expression patterns in embryonic pad lamellae and dorsal epidermis. It is inferred that glycine-rich CBPs are integral to the formation of both dorsal scales and lamellar setae, cysteine-rich CBPs are primarily associated with setae development. Additionally, fluorescence in situ hybridization revealed spatiotemporal differences in the expression of a glycine-rich CBP encoding gene (ge-gprp-19) and a cysteine-rich CBP encoding gene (ge-cprp-17) during dorsal scales and/or lamellar development. CONCLUSIONS: All 66 CBPs are involved in the formation of setae. Glycine-rich CBPs hold a significant role in the development of dorsal scales and lamellar setae, whereas most cysteine-rich CBPs appear to be essential components of G. japonicus setae. Even GjCBPs with similar amino acid compositions may play diverse functions. The clear spatio-temporal expression differences between the glycine-rich and cysteine-rich CBP encoding genes during epidermal scale and/or setae formation were observed. Embryonic developmental stages 39 to 42 emerged as crucial phases for setae development. These findings lay the groundwork for deeper investigation into the function of GjCBPs in the development of G. japonicus setae.

Chemical Constituents from Berchemia polyphylla var. Leioclada.

One previously undescribed naphthoquinone-benzisochromanquinone dimer berpolydiquinone A (1), along with two previously undescribed naphthoquinone-anthraquinone dimers berpolydiquinones B and C (2-3), and one previously undescribed dimeric naphthalene berpolydinaphthalene A (4), were isolated from the stems and leaves of Berchemia polyphylla var. leioclada. The chemical structures of these compounds were determined using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), spectroscopic data, the exciton chirality method (ECM), and quantum chemical calculation. Notably, compounds (1-2 and 5) are dimeric quinones that share the same naphthoquinone moiety, specifically identified as 2-methoxystypandron. Compound (4) is a derivative of dimeric naphthalene with a symmetrical structure, which is a new structure type isolated from B. polyphylla var. leioclada for the first time. These findings suggest that B. polyphylla var. leioclada serves as a significant reservoir of structurally diverse phenolic compounds. This study provides a scientific foundation for regarding B. polyphylla var. leioclada as a potential source of "Tiebaojin".

Anthraquinone-benzisochromanquinone dimers from the stems and leaves of Berchemia polyphylla.

Three new anthraquinone-benzisochromanquinone dimers polyphylldiquinones A-C (1-3), along with three known analogs floribundiquinone A-B (4-5) and 7-dehydroxyventiloquinone H (6), were isolated from the stems and leaves of Berchemia polyphylla. The chemical structures and absolute configurations of these compounds were determined using HR-ESI-MS, spectroscopic data, and electronic circular dichroism. Notably, compounds (1-5) are dimeric quinones that share the same benzisochromanquinone moiety, specifically identified as 7-dehydroxyventiloquinone H (6), which was the first time to report as a natural product. Compounds 1-2 and compounds 4-5 are two pairs of atropisomers respectively.

Molecular Subtypes of Ovarian Cancer Based on Lipid Metabolism and Glycolysis Reveals Potential Therapeutic Targets.

BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecological malignant neoplasms. The aim of this study was to use high-throughput sequencing data to investigate the molecular and clinical characteristics of OC subtypes related to lipid metabolism and glycolysis, thus providing a theoretical basis for clinical decision-making. METHODS: Molecular data and clinicopathological characteristics of OC patients were extracted from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), and the Gene Expression Omnibus (GEO). Following analysis of genes involved in lipid metabolism and glycolysis, OC was classified into subtypes by unsupervised clustering. The molecular features and clinical outcomes of these subtypes were then evaluated. RESULTS: OC patients were divided into five subtypes based on the analysis of nine genes of interest. Amongst these, patients in subtype D had longer overall survival and more benign clinical features. Subtypes B and E had shorter overall- and progression-free survival, respectively. Both the B and E subtypes were closely related to lipid metabolism and to the glycolytic process. Subtype D was positively correlated with the infiltration of CD8+ T cells, CD4+ T cells, and macrophages, all of which play essential anti-tumor roles. Several risk models for selected subtypes were also constructed based on the expression of select genes. CONCLUSIONS: The present work revealed that irregular metabolism in OC tissues was an indicator of poor clinical outcome and altered homeostasis in cancer-related pathways. Moreover, aberrant gene expression signatures associated with lipid metabolism and glycolysis were also correlated with an immunosuppressive tumor microenvironment. Based on lipid metabolism and glycolysis, we have therefore identified several OC molecular subtypes that may prove useful for the development of potential therapeutic targets.

A comprehensive review of the family of very-long-chain fatty acid elongases: structure, function, and implications in physiology and pathology.

BACKGROUND: The very-long-chain fatty acid elongase (ELOVL) family plays essential roles in lipid metabolism and cellular functions. This comprehensive review explores the structural characteristics, functional properties, and physiological significance of individual ELOVL isoforms, providing insights into lipid biosynthesis, cell membrane dynamics, and signaling pathways. AIM OF REVIEW: This review aims to highlight the significance of the ELOVL family in normal physiology and disease development. By synthesizing current knowledge, we underscore the relevance of ELOVLs as potential therapeutic targets. KEY SCIENTIFIC CONCEPTS OF REVIEW: We emphasize the association between dysregulated ELOVL expression and diseases, including metabolic disorders, skin diseases, neurodegenerative conditions, and cancer. The intricate involvement of ELOVLs in cancer biology, from tumor initiation to metastasis, highlights their potential as targets for anticancer therapies. Additionally, we discuss the prospects of using isoform-specific inhibitors and activators for metabolic disorders and cancer treatment. The identification of ELOVL-based biomarkers may advance diagnostics and personalized medicine. CONCLUSION: The ELOVL family's multifaceted roles in lipid metabolism and cellular physiology underscore its importance in health and disease. Understanding their functions offers potential therapeutic avenues and personalized treatments.

Time-Related Vascular Inflammatory Response to COVID-19 Assessed by 18F-FDG PET/CT in Follow-Up Tumor Patients.

Purpose: This study aimed to assess COVID-19's effects on vascular inflammatory response, by evaluating 18-Fluorodeoxyglucose (18F-FDG) uptake via positron emission tomography/computed tomography (PET/CT) in the artery of diffuse large B cell lymphoma (DLBCL) patients before and after infection with COVID-19. Patients and Methods: Thirty-five DLBCL patients administered the chemotherapy regimen R-CHOP and examined by oncological 18F-FDG PET/CT imaging twice from August 2022 to February 2023 for pre-treatment evaluation or assessment of treatment efficacy were enrolled. Seventeen patients were confirmed with COVID-19 within the study period. Arterial wall FDG uptake was semi-quantitatively analyzed as TBR (target-to-blood pool ratio) in 14 different vascular regions using oncological 18F-FDG PET/CT. Based on COVID-19 course and the two PET/CT scans, we further analyzed time-related FDG uptake for vascular walls in DLBCL patients with COVID-19. Results: Arterial TBRs were higher in the last PET/CT examination than previous ones in all patients with or without COVID-19. Besides the ascending aorta, ΔTBR (last PET/CT scanning's TBR minus previous PET/CT scanning's TBR) were not significantly different between the COVID-19 and Control groups. However, cases scanned ≤30 days from infection had remarkably higher ΔTBRs in comparison with those assessed >30 days post-infection in the COVID-19 group (p<0.05). A moderate inverse correlation was observed between ∆Global TBR (last PET/CT scanning's average TBR value minus previous PET/CT scanning's average TBR value) and time distance from COVID-19 onset to 18F-FDG PET/CT scan (Spearman's rho=-0.591, P=0.012). Interestingly, there were no differences of changes of TBR between different purpose of PET/CT examination group. Conclusion: This work firstly suggested vascular inflammation is elevated in the early post-COVID-19 phase in DLBCL cases compared with prolonged post-COVID-19 phase or controls. Increasing attention should be paid to these patients and the protection of their vascular function and complications in early COVID-19.

Structural and electronic properties of H2, CO, CH4, NO, and NH3 adsorbed onto Al12Si12 nanocages using density functional theory.

In this study, the adsorption of gases (CH4, CO, H2, NH3, and NO) onto Al12Si12 nanocages was theoretically investigated using density functional theory. For each type of gas molecule, two different adsorption sites above the Al and Si atoms on the cluster surface were explored. We performed geometry optimization on both the pure nanocage and nanocages after gas adsorption and calculated their adsorption energies and electronic properties. The geometric structure of the complexes changed slightly following gas adsorption. We show that these adsorption processes were physical ones and observed that NO adsorbed onto Al12Si12 had the strongest adsorption stability. The E g (energy band gap) value of the Al12Si12 nanocage was 1.38 eV, indicating that it possesses semiconductor properties. The E g values of the complexes formed after gas adsorption were all lower than that of the pure nanocage, with the NH3-Si complex showing the greatest decrease in E g. Additionally, the highest occupied molecular orbital and the lowest unoccupied molecular orbital were analyzed according to Mulliken charge transfer theory. Interaction with various gases was found to remarkably decrease the E g of the pure nanocage. The electronic properties of the nanocage were strongly affected by interaction with various gases. The E g value of the complexes decreased due to the electron transfer between the gas molecule and the nanocage. The density of states of the gas adsorption complexes were also analyzed, and the results showed that the E g of the complexes decreased due to changes in the 3p orbital of the Si atom. This study theoretically devised novel multifunctional nanostructures through the adsorption of various gases onto pure nanocages, and the findings indicate the promise of these structures for use in electronic devices.

The clinical value of the Controlling Nutritional Status score for predicting prognosis in systolic heart failure cases in the vulnerable phase.

Background: Malnutrition, a commonly encountered complication of heart failure, has an association with poor prognosis. The vulnerable phase of heart failure constitutes the most vulnerable stage of heart failure cases after discharge (usually within 3 months). At present, the prognostic value of Controlling Nutritional Status (CONUT) score in the vulnerable phase of systolic heart failure is unclear. Methods: Totally 187 systolic heart failure cases were retrospectively assessed at the Second Affiliated Hospital of Dalian Medical University. Based on CONUT score at admission, cases were assigned to 3 groups, including the normal nutrition, and mild and moderate or severe malnutrition groups. The primary endpoint was all-cause death in the 90 days following discharge. The secondary, composite outcome encompassed all-cause death and rehospitalization due to heart failure. Kaplan-Meier method and log-rank test were performed to compare outcome event rates between groups. The independent risk factors for outcome events were obtained by multivariate COX regression analysis. The receiver operating characteristic (ROC) curve analysis and the Delong test were used to compare the prediction performance of the CONUT score and other independent risk factors for all-cause death. Results: During the 90 days of follow-up, 8.6% of HF patients had the primary endpoint and 23.5% had the secondary outcome. All-cause mortality was markedly elevated in the moderate or severe malnutrition group (Logrank: p < 0.001). Compared with the normal nutrition group, composite endpoint events had starkly increased incidence rates in both malnutrition groups, and the incidence increased with the severity of malnutrition (Logrank: p < 0.05). Multivariate COX risk analysis revealed higher CONUT score [hazard ratio (HR) = 1.791, 95% confidence interval (CI) 1.379-2.327], age (HR = 1.08, 95% CI 1.028-1.134), B-type natriuretic peptide (BNP) (HR = 1.001, 95% CI 1.000-1.001), and aspartate aminotransferase (AST) (HR = 1.008, 95% CI 1.001-1.015) at admission as independent predictive factors of all-cause mortality. And higher CONUT score (HR = 1.162, 95% CI 1.024-1.318) and lower estimated glomerular filtration rate (eGFR) (HR = 0.98, 95% CI 0.966-0.993) for the secondary endpoint. The addition of the CONUT score significantly increased the predictive performance of age, BNP and AST, as well as their combination for all-cause death (Delong test: all p < 0.05). Conclusion: The CONUT score at admission independently predicts poor prognosis during the vulnerable phase in patients with systolic heart failure and may be combined with conventional risk factors to further improve the predictive efficacy.

The Correlation between Increased Expressions of NLRP3 Inflammasome Components in Peripheral Blood Mono-Nuclear Cells and Plaque Vulnerability in Human Carotid Atherosclerosis.

Background: We aimed to determine whether NLRP3 inflammasomes in peripheral blood mononuclear cells (PBMC) were associated with carotid plaque instability in carotid atherosclerosis patients. Methods: Consecutive 38 carotid atherosclerosis with vulnerable plaques, 22 carotid atherosclerosis with stable plaques, and 40 healthy subjects with no carotid or coronary artery stenosis were enrolled. They were referred to the Second Hospital of Dalian Medical University from 2013-2019. Carotid plaques were evaluated by modified plaque vulnerability risk score (MPVRS) and pathological assessment. The mRNA and protein expression of NLRP3 inflammasome components in PBMC were determined by quantitative real time PCR and Western blot analysis or ELISA. Results: When consecutive study subjects undergoing carotid endarterectomy were divided into stable (≤4) and unstable (>4) plaque groups according to the MPVRS, the unstable plaque group had significantly raised mRNA and protein expression of NLRP3 inflammasome components in PBMC as compared with the stable plaque group and healthy subject group. Furthermore, subjects with higher NLRP3 protein expression in PBMC had greater incidence of cerebrovascular events. Conclusion: Increased NLRP3 inflammasome components in PBMC is associated with instability of human carotid atherosclerotic plaques, suggesting NLRP3 inflammasome as a potential biomarker for monitoring carotid plaque instability.

Scalemic diacetylenic spiroacetal enol ethers from the flowers of Tanacetum tatsienense.

Six scalemic mixtures of previously undescribed diacetylenic spiroacetal enol ethers (DSEEs) and six scalemic mixtures of known DSEEs were isolated from the flowers of Tanacetum tatsienense. Except for E-epidendranthemenol, Z-O-acetyl-epi dendranthemenol, and Z-O-isovaleryl-epidendranthemenol, the remaining scalemic mixtures of DSEEs were resolved by chiral HPLC, and their structures were determined through an analysis of HR-ESI-MS and NMR data. The absolute configurations of seven pairs of enantiomers and one pair of epimers were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. In addition, the inhibitory effects of all of the DSEEs on nitric oxide (NO) production were evaluated in LPS-stimulated RAW264.7 cells. The results showed that (+)-tatsienenol B had a weak inhibitory effect on NO production. The IC50 value of the compound was 19.78 ±â€¯0.78 µM. This study is the first to report that DSEEs are isolable from plants as scalemic mixtures. Moreover, this study is the first to determine the absolute configurations of DSEEs by chiral resolution and ECD calculations.

How leaders' bias tendency affects employees' knowledge hiding behavior: The mediating role of workplace marginalization perception.

Employees' knowledge hiding behavior has an essential inhibitory impact on organizational innovation and employee knowledge sharing. Accordingly, studying the antecedents and influencing mechanisms of employees' knowledge hiding behavior is quite necessary. In the perspective of leader-member exchange theory and resource conservation theory, the leaders' bias tendency will lead to the workplace marginalization perception of some employees and promote the generation of employees' knowledge hiding behavior. Thus, this research is intended to discuss the influence of leaders' bias tendency toward employees' knowledge hiding behavior, and to analyze the mediating effects of employees' perception of workplace marginalization and the moderating role of emotional commitment to the organization. The sample of this study covered 500 Chinese full-time corporate employees. The conclusions of the research indicate that the following: (1) Leaders' bias tendency is vitally and absolutely correlated with employees' knowledge hiding behavior; (2) Workplace marginalization perception plays an intermediary role between leaders' bias tendency and employees' knowledge hiding behavior; (3) Emotional commitment to the organization plays a negative moderating role between leaders' bias tendency and employees' knowledge hiding behavior; (4) Emotional commitment to the organization plays a negative moderating role between workplace marginalization perception and employees' knowledge hiding behavior. These findings will help organizations and managers to recognize the harm of bias tendency, regulate their own behaviors, and effectively reduce the generation of employees' knowledge hiding behaviors, thereby promoting knowledge sharing and innovative behaviors in organizations.

Chemical constituents from the seeds of Nigella glandulifera and their hypoglycemic activities.

The seeds of Nigella glandulifera Freyn et Sint. are traditional Uygur medicine used for the treatment of diabetes. However, the active anti-diabetic constituents in the seeds of N. glandulifera remain unclear. In the present study, a new delabellane-type diterpene, 8-denicotinoylnigellamine A1 (1), and a new acyclic sesquiterpene, 2,6,10-trimethyl-6,7,12-trihydroxy-dodec-2-ene (3), together with eight known compounds including alkaloids (2 and 7), triterpenoid saponins (4-6), and phenolic compounds (8-10), were isolated from the seeds of N. glandulifera. Their structures were determined by extensive spectroscopic analyses and quantum chemical calculations. We evaluated the potential protective effects of the isolated compounds on an insulin resistant HepG2 (IR-HepG2) cell model. The results showed that compounds 2, 4-8, and 10 could promote the consumption of glucose in IR-HepG2 cells. Those compounds might be responsible for the anti-diabetic effects of the seeds of N. glandulifera.

A bifunctional GeC/SnSSe heterostructure for highly efficient photocatalysts and photovoltaic devices.

Alongside highly efficient photocatalysts, high photovoltaic performance is also a key element for efficiently harvesting solar energy. Developing bifunctional materials which satisfy concurrently these two demands is an appealing strategy for solving the current serious energy and environmental issues. Based on first-principles and quantum transport calculations, we designed this kind of novel bifunctional material: Janus GeC/SnSSe van der Waals heterostructure (vdWH). We demonstrate that it is a highly efficient direct Z-scheme photocatalyst. However, unlike traditional direct Z-scheme photocatalysts, the GeC/SnSSe vdWH possesses a small energy separation between the low conduction band located in SnSSe and the high valence band residing in the GeC layer, which significantly fosters the interlayer charge transfer. Hence, its solar-to-hydrogen conversion efficiency reaches as high as 68.37%. Moreover, we also find that tensile strain promotes an astonishing increase in photovoltaic performance, e.g., 4% tensile strain leads to an increase of the photocurrent by 40%.

Phenolic Compounds From the Stems and Leaves of Berchemia lineata (L.) DC.

Eight new phenolic compounds, named bercheminols A-H (1-8), and eleven known analogues were isolated from the stems and leaves of Berchemia lineata (L.) DC. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, chemical method, and quantum chemical calculations. Compound 1 possesses an unprecedented 3,4-dihydro-11H-benzo[b]pyrano[4,3-e] oxepin-11-one skeleton. The other new compounds belong to three structural types of natural products, including naphthopyrones (2-5), flavonoids (6-7), and bibenzyl (8). The α-glucosidase inhibitory activities of the isolated compounds were assayed. As a result, vittarin-B (9), rubrofusarin-6-O-ß-D-glucopyranoside (11), quercetin (14), kaempferol (15), and dihydrokaempferol (17) showed moderate inhibitory activities against α-glucosidase with IC50 values of 22.5, 28.0, 36.5, 32.7, and 31.9 µM, respectively.

The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment.

The tumor microenvironment (TME) is related to chronic inflammation and is currently identified as a risk factor for the occurrence and development of endometrial cancer (EC). Pyroptosis is a new proinflammatory form of programmed cell death that plays a critical role in the progression of multiple diseases. However, the important role of pyroptosis in high-glucose (HG)-related EC and the underlying molecular mechanisms remain elusive. In the present study, transcriptome high-throughput sequencing revealed significantly higher hexokinase domain-containing 1 (HKDC1) expression in EC patients with diabetes than in EC patients with normal glucose. Mechanistically, HKDC1 regulates HG-induced cell pyroptosis by modulating the production of reactive oxygen species and pyroptosis-induced cytokine release in EC. In addition, HKDC1 regulates TME formation by enhancing glycolysis, promoting a metabolic advantage in lactate-rich environments to further accelerate EC progression. Subsequently, miR-876-5p was predicted to target the HKDC1 mRNA, and HOXC-AS2 was identified to potentially inhibit the miR-876-5p/HKDC1 axis in regulating cell pyroptosis in HG-related EC. Collectively, we elucidated the regulatory role of the HOXC-AS2/miR-876-5p/HKDC1 signal transduction axis in EC cell pyroptosis at the molecular level, which may provide an effective therapeutic target for patients with diabetes who are diagnosed with EC.

Polyprenylated Acylphloroglucinols With Different Carbon Skeletons From the Fruits of Garcinia multiflora.

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-11) and three new monocyclic polyprenylated acylphloroglucinols (MPAPs, 12-14), together with ten known analogues were isolated from the fruits of Garcinia multiflora. These PPAPs belong to three types including the bicyclic polyprenylated acylphloroglucinols (BPAPs), the caged PPAPs, and the complicated PPAPs. Their structures and absolute configurations were determined through HRESIMS, NMR spectroscopy data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations with DP4+ analyses. Moreover, compounds 2 and 7 exhibited moderate cytotoxicity against three human cancer lines (MCF-7, T98, and HepG2) with IC50 values ranging from 9.81 ± 1.56 to 17.00 ± 2.75 µM.

Discovery of Novel Polycyclic Polyprenylated Acylphloroglucinols from the Fruits of Garcinia xanthochymus as Antitumor Agents by Suppressing the STAT3 Signaling.

Pharmacologic studies have revealed that polycyclic polyprenylated acylphloroglucinols (PPAPs) collectively exhibit a broad range of biological activities, including antineoplastic potential. Here, six new PPAPs, named garcixanthochymones F-K (3, 5, 7, 8, 11, and 15), together with nine known analogues were isolated from the fruits of Garcinia xanthochymus. Their structures were elucidated based on the spectroscopic data, including UV, HRESIMS, and NMR, and quantum chemical calculations. All the isolated PPAPs were tested for anti-proliferative activity against four human tumor cell lines, including SGC7901, A549, HepG2, and MCF-7. Most of the PPAPs possessed high anti-proliferative activity with IC50 values in the range of 0.89 to 36.98 µM, and significant apoptosis was observed in MCF-7 cells exposed to compounds 2 and 5. Besides, docking results showed that compounds 2 and 5 could strongly combine with the Src homology 2 (SH2) domain of STAT3 via hydrogen bond and hydrophobic interaction, which is one of the key oncogenes and crucial therapeutic targets. Furthermore, compounds 2 and 5 efficiently downregulated the expression of p-STAT3Tyr705 and pivotal effector proteins involved in oncogenic signaling pathways of MCF-7 cells.

Wilms' Tumor 1-Associated Protein Contributes to Chemo-Resistance to Cisplatin Through the Wnt/ß-Catenin Pathway in Endometrial Cancer.

BACKGROUND: Cisplatin remains the mainstay of endometrial cancer (EC) chemotherapy. Wilms' tumor 1-associated protein (WTAP), playing a critical role in transcriptional and post-transcriptional regulation, has been reported as an oncogene, and its expression is elevated in multiple types of human tumors. Recent evidence has shown that the increased expression of WTAP is also closely related to chemo-resistance. However, its specific role in the susceptibility of human EC cells to cisplatin remains largely unexplored. METHODS: WTAP over-expression and WTAP depletion cell lines as well as their corresponding controls were constructed by transfection with lentivirus. Western blotting analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to detect the expression of WTAP. Cell proliferation assay, colony formation assay, cell cycle assay, and apoptosis analysis were adopted to evaluate the effect of WTAP on the chemo-sensitivity of EC cells to cisplatin as well as its underlying mechanism. Immunofluorescence staining was used to assess the translocation of ß-catenin. Moreover, a subcutaneous xenograft tumor model was established to assess the effect of WTAP on tumor growth after cisplatin treatment. RESULTS: Depletion of WTAP in RL95-2 cells significantly enhanced the chemo-susceptibility of cells to cisplatin and increased the cell apoptosis, while WTAP over-expression in ARK-2 cells exhibited the opposite effects. Additionally, WTAP depletion significantly suppressed xenograft-tumor growth and enhanced sensitivity and apoptosis of tumor cells in vivo. Mechanistic analysis exhibited that WTAP over-expression facilitated the cytoplasm-to-nucleus translocation of ß-catenin and enhanced the GSK3ß phosphorylation at Ser9, while WTAP depletion revealed the opposite results, indicating that WTAP rendered chemo-resistance of EC cells to cisplatin by promoting the Wnt/ß-catenin pathway. CONCLUSIONS: WTAP might promote the chemo-resistance of EC cells to cisplatin through activating the Wnt/ß-catenin pathway. Collectively, our findings offered novel insights into EC treatment.