Exploration of the role of EMC3­AS1 as a potential diagnostic and prognostic indicator in liver cancer.

The aim of the present study was to evaluate the diagnostic and prognostic significance of the long non-coding RNA (lncRNA) endoplasmic reticulum membrane protein complex subunit 3 antisense RNA 1 (EMC3-AS1) in liver cancer, and its impact on the proliferative and invasive capabilities of liver cancer cells. EMC3-AS1 expression in liver cancer was assessed using data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets, and validated in clinical liver cancer samples using reverse transcription-quantitative PCR. The prognostic and diagnostic potentials of this lncRNA were evaluated using Kaplan-Meier and receiver operating characteristic analyses, respectively. The infiltration of immune cells and differential expression of immune checkpoints (ICs) between high- and low-EMC3-AS1 expression groups were investigated. Therapeutic correlation analyses were also undertaken to assess the impact of EMC3-AS1 in the treatment of liver cancer. In addition, in vitro experiments were conducted using small interfering RNA to knock down the expression of EMC3-AS1 in HepG2, Sk-Hep-1 and Huh-7 cells, and evaluate the effect on cell proliferation, colony formation and migration. The results revealed a significant upregulation of EMC3-AS1 expression in liver cancer tissues compared with that in adjacent normal tissues, which was associated with an unfavorable prognosis and demonstrated diagnostic effectiveness for patients with liver cancer. Furthermore, patients with high EMC3-AS1 expression exhibited increased levels of IC markers in comparison with those with low EMC3-AS1 expression. In addition, EMC3-AS1 was indicated to have clinical significance in the prediction of the response to immunotherapy and chemotherapy. Notably, the in vitro experiments demonstrated that the knockdown of EMC3-AS1 significantly hindered cell proliferation, colony formation and migration. Consequently, it was concluded that EMC3-AS1 is upregulated in liver cancer and serves as a prognostic indicator for unfavorable outcomes in patients with liver cancer. Additionally, targeting EMC3-AS1 through knockdown interventions showed potential in mitigating the ability of liver cancer cells to proliferate and migrate, which highlights its dual role as a biomarker and therapeutic target for liver cancer.

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress.

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000 mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000 mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100 mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What's more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

Correction: Aptamer AS1411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

[This corrects the article DOI: 10.1039/D3MD00752A.].

Aptamer AS411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

G-quadruplex (G4) aptamers that can competitively binding protein with oncogene promoter G4 hold promise for cancer treatment. In this study, a neutral cytidinyl lipid, DNCA, was shown to transfect and deliver G4 aptamers (AS1411, TBA) into tumour cells, including multidrug-resistant tumour cells, and their nuclear localizations were clearly detected. Both AS1411/DNCA and TBA/DNCA showed excellent antitumour efficacies in the drug-resistant non-small cell lung cancer cell line A549/TXL at a low concentration (100 nM). Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as a new target of AS1411 and TBA. The binding affinities were measured, and the Kd values of AS1411/hnRNP A1 and TBA/hnRNP A1 were 17.5 nM and 21.1 nM, respectively. Then the expression of KRAS mRNA in A549/TXL cells was found to be higher than that in A549 cells, and KRAS mRNA was reduced by approximately 40% after administration of AS1411 or TBA in A549/TXL cells. Further, it was confirmed for the first time that AS1411 targeted not only hnRNP A1 but also the KRAS promoter/hnRNP A1 complexes. And although TBA cannot target the KRAS promoter/hnRNP A1 complexes, the biolayer interferometry (BLI) experiment showed that TBA and AS1411 have similar effects on several key proteins in tumour cells, especially hnRNP A1. Molecular docking and molecular dynamics simulation showed that AS1411 and the KRAS promoter bound to the same domain of hnRNP A1 protein, while TBA bound to another domain.

The Janus face of HIF-1α in ischemic stroke and the possible associated pathways.

Stroke is the most devastating disease, causing paralysis and eventually death. Many clinical and experimental trials have been done in search of a new safe and efficient medicine; nevertheless, scientists have yet to discover successful remedies that are also free of adverse effects. This is owing to the variability in intensity, localization, medication routes, and each patient's immune system reaction. HIF-1α represents the modern tool employed to treat stroke diseases due to its functions: downstream genes such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Its role can be achieved via two downstream EPO and VEGF strongly related to apoptosis and antioxidant processes. Recently, scientists paid more attention to drugs dealing with the HIF-1 pathway. This review focuses on medicines used for ischemia treatment and their potential HIF-1α pathways. Furthermore, we discussed the interaction between HIF-1α and other biological pathways such as oxidative stress; however, a spotlight has been focused on certain potential signalling contributed to the HIF-1α pathway. HIF-1α is an essential regulator of oxygen balance within cells which affects and controls the expression of thousands of genes related to sustaining homeostasis as oxygen levels fluctuate. HIF-1α's role in ischemic stroke strongly depends on the duration and severity of brain damage after onset. HIF-1α remains difficult to investigate, particularly in ischemic stroke, due to alterations in the acute and chronic phases of the disease, as well as discrepancies between the penumbra and ischemic core. This review emphasizes these contrasts and analyzes the future of this intriguing and demanding field.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

A Real-World Retrospective Study to Evaluate the Reliability of Cetuximab plus Capecitabine versus Capecitabine as Maintenance Therapy in Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer.

BACKGROUND: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). PATIENTS AND METHODS: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. RESULTS: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4-12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8-8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. CONCLUSION: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients.

Prohibitin 2: A key regulator of cell function.

The PHB2 gene is located on chromosome 12p13 and encodes prohibitin 2, a highly conserved protein of 37 kDa. PHB2 is a dimer with antiparallel coils, possessing a unique negatively charged region crucial for its mitochondrial molecular chaperone functions. Thus, PHB2 plays a significant role in cell life activities such as mitosis, mitochondrial autophagy, signal transduction, and cell death. This review discusses how PHB2 inhibits transcription factors or nuclear receptors to maintain normal cell functions; how PHB2 in the cytoplasm or membrane ensures normal cell mitosis and regulates cell differentiation; how PHB2 affects mitochondrial structure, function, and cell apoptosis through mitochondrial intimal integrity and mitochondrial autophagy; how PHB2 affects mitochondrial stress and inhibits cell apoptosis by regulating cytochrome c migration and other pathways; how PHB2 affects cell growth, proliferation, and metastasis through a mitochondrial independent mechanism; and how PHB2 could be applied in disease treatment. We provide a theoretical basis and an innovative perspective for a comprehensive understanding of the role and mechanism of PHB2 in cell function regulation.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

ceRNA network-regulated COL1A2 high expression correlates with poor prognosis and immune infiltration in colon adenocarcinoma.

Collagen type I α 2 (COL1A2) is a major component of collagen type I. Recently, abnormal COL1A2 expression has been reported in human cancers. However, the specific role and mechanism of COL1A2 in colon adenocarcinoma (COAD) remain unclear. We performed the pan-cancer analysis of COL1A2 expression in 33 types of human cancers from TIMER database and integrated data combined TCGA with GTEx. The prognostic values of COL1A2 for 17 cancer types of interest were estimated from GEPIA database. The results showed that COL1A2 was significantly upregulated in COAD tissues and that higher COL1A2 expression predicted unfavorable prognosis for patients with COAD. Next, COL1A2-related functional pathways in COAD were analyzed with TCGA data using R package. Additionally, we constructed a ceRNA network that LINC00638/hsa-miR-552-3p axis served as a potential regulatory pathway of COL1A2 in COAD. Furthermore, our findings showed that COL1A2 positively associated with immune infiltration and that tumor immune escape might be involved in COL1A2-mediated carcinogenesis in COAD. For the first time, we constructed a ceRNA prediction network of COL1A2 and explored the association of COL1A2 with tumor immune microenvironment remodeling. The findings may advance our understanding of the pathogenesis mechanism in COAD and paves the way for further cancer therapeutics.

Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) show podocyte-protective effects in chronic kidney disease. Calycosin (CA), a phytoestrogen, is isolated from Astragalus membranaceus with a kidney-tonifying effect. CA preconditioning enhances the protective effect of MSCs against renal fibrosis in mice with unilateral ureteral occlusion. However, the protective effect and underlying mechanism of CA-pretreated MSCs (MSCsCA) on podocytes in adriamycin (ADR)-induced focal segmental glomerulosclerosis (FSGS) mice remain unclear. AIM: To investigate whether CA enhances the role of MSCs in protecting against podocyte injury induced by ADR and the possible mechanism involved. METHODS: ADR was used to induce FSGS in mice, and MSCs, CA, or MSCsCA were administered to mice. Their protective effect and possible mechanism of action on podocytes were observed by Western blot, immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction. In vitro, ADR was used to stimulate mouse podocytes (MPC5) to induce injury, and the supernatants from MSC-, CA-, or MSCsCA-treated cells were collected to observe their protective effects on podocytes. Subsequently, the apoptosis of podocytes was detected in vivo and in vitro by Western blot, TUNEL assay, and immunofluorescence. Overexpression of Smad3, which is involved in apoptosis, was then induced to evaluate whether the MSCsCA-mediated podocyte protective effect is associated with Smad3 inhibition in MPC5 cells. RESULTS: CA-pretreated MSCs enhanced the protective effect of MSCs against podocyte injury and the ability to inhibit podocyte apoptosis in ADR-induced FSGS mice and MPC5 cells. Expression of p-Smad3 was upregulated in mice with ADR-induced FSGS and MPC5 cells, which was reversed by MSCCA treatment more significantly than by MSCs or CA alone. When Smad3 was overexpressed in MPC5 cells, MSCsCA could not fulfill their potential to inhibit podocyte apoptosis. CONCLUSION: MSCsCA enhance the protection of MSCs against ADR-induced podocyte apoptosis. The underlying mechanism may be related to MSCsCA-targeted inhibition of p-Smad3 in podocytes.

Comparing genomes of Fructus Amomi-producing species reveals genetic basis of volatile terpenoid divergence.

Wurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are 2 primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoid divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contributes to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae.

Diagnostic accuracy of circulating exosomal circRNAs in malignances: A meta-analysis and systematic review.

BACKGROUND: Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. RESULTS: Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies. CONCLUSIONS: In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.

Effects of Ethylene-Propylene-Diene Monomers (EPDMs) with Different Moony Viscosity on Crystallization Behavior, Structure, and Mechanical Properties of Thermoplastic Vulcanizates (TPVs).

Moony viscosity of ethylene-propylene-diene monomers (EPDMs) can have effect on the crystallization dynamics, structure, and properties of EPDM/polypropylene (PP)-based thermoplastic vulcanizates (TPVs). TPVs with two different Moony viscosities are prepared via a twin-screw extruder, respectively. Crosslinked EPDM with lower Moony viscosity has a higher crosslinking density and the nucleation effect of its crosslink point improves the crystallization ability of PP in TPV, leading to PP phase crystallization at higher temperatures. For TPV with an EPDM of higher Moony viscosity, it has higher crystallinity and the EPDM phase crystallized earlier. Synchrotron radiation studies show that the EPDM with low Moony viscosity has no obvious crystalline structure, and the prepared TPV has an obvious phase separation structure, while the TPV with higher Mooney viscosity of the EPDM does not exhibit obvious phase separation, indicating that the longer EPDM chains have better compatibility with PP in TPV, also evidenced by the almost disappearance of the PP glass transition peak in TPV, from the dynamic mechanical analysis. The longer EPDM chains in TPV provide more physical entanglement and better interaction with PP molecules, resulting in a stronger strain hardening process, longer elongation at break, and higher tensile stress in TPV.

Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Comparison of the anesthesia effect of ultrasound-guided middle and low interscalene brachial plexus block: a randomized, controlled, non-inferiority trial.

BACKGROUND: Ultrasound-guided low interscalene brachial plexus block (LISB) can provide satisfactory anesthesia for surgery at or below the elbow. However, the anesthesia effect of ultrasound-guided middle interscalene brachial plexus block (MISB) has not been fully investigated. We hypothesized that MISB provides a non-inferior anesthesia effect to LISB for surgery at or below the elbow. METHODS: A total of 82 patients with ASA I-III (18-65 years) scheduled for elective surgery at or below the elbow were randomized to the MISB group or the LISB group equally, located 1/2 or 2/3 of the caudal distance from C6 to the clavicle. Both groups were administered 15 mL 0.5% ropivacaine at the lower part of the brachial plexus with the first injection and equivalent volume at the upper part with the second injection. RESULTS: For the primary outcome, 92.3% in the MISB group experienced successful anesthesia compared to 94.6% in the LISB group [difference: -2.3%, 95% confidence interval (CI) -13.4% to 8.8%], exceeding the predefined non-inferiority margin -15%. For the secondary outcomes, the incidence of pleura suppression for the first injection (7.7% vs. 45.9%, P < 0.001) and the time to perform the block (9.9 ± 1.3 vs. 10.7 ± 1.3 min, P = 0.006) were significantly less in MISB compared to LISB. No significant differences were observed in the consumption of perioperative rescue analgesics, VAS score, and adverse events within the two groups. CONCLUSIONS: MISB provides a non-inferior anesthesia effect to LISB for surgery at or below the elbow. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2100054196).

JMJD3 Is Required for Acute Pancreatitis and Pancreatitis-Associated Lung Injury.

Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.

The association between outdoor air pollution and lung cancer risk in seven eastern metropolises of China: Trends in 2006-2014 and sex differences.

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, µg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.

Ammonia promotes the proliferation of bone marrow-derived mesenchymal stem cells by regulating the Akt/mTOR/S6k pathway.

Ammonia plays an important role in cellular metabolism. However, ammonia is considered a toxic product. In bone marrow-derived mesenchymal stem cells, multipotent stem cells with high expression of glutamine synthetase (GS) in bone marrow, ammonia and glutamate can be converted to glutamine via glutamine synthetase activity to support the proliferation of MSCs. As a major nutritional amino acid for biosynthesis, glutamine can activate the Akt/mTOR/S6k pathway to stimulate cell proliferation. The activation of mTOR can promote cell entry into S phase, thereby enhancing DNA synthesis and cell proliferation. Our studies demonstrated that mesenchymal stem cells can convert the toxic waste product ammonia into nutritional glutamine via GS activity. Then, the Akt/mTOR/S6k pathway is activated to promote bone marrow-derived mesenchymal stem cell proliferation. These results suggest a new therapeutic strategy and potential target for the treatment of diseases involving hyperammonemia.