Innovation, advertising, personal selling, and sustainability in the industries massively benefited from major public health emergencies: paradoxical evidence from China.

Background: While major public health emergencies have severe socio-economic impacts, they may also present many opportunities for certain industries. For these industries that have benefited significantly (e.g., China' s healthcare industry), the traditional emphasis on improving business performance through increased investment in innovation, marketing and sustainability may face contextual applicability challenges. Methods: We used the data of healthcare industry in China during Covid-19 and the methods of hierarchical regression, moderating effect test to analyze the impact of innovation, advertising, personal selling, and sustainability on healthcare firms' profitability. Three kinds of robust test including increasing the measurement range of variables, changing the data source and parameter estimation method, and Quantile regression are used. Results: This paper finds that innovation, advertising, and environmental sustainability have significant negative impacts on profitability, while personal selling, social sustainability, and governance sustainability have significant positive impacts on profitability in the industries massively benefited from major public health emergencies. Besides, social sustainability can significantly moderate the relationship between innovation and profitability. Conclusion: On one hand, for companies in industries that have benefited greatly from major public health emergencies, a shift in resource allocation from innovation, advertising, and environmental sustainability to personal selling, social sustainability, and governance sustainability may be more conducive to improving their profitability. On the other hand, for public health regulatory authorities, it is necessary to strengthen the supervision of sales representatives of health care enterprises, hospitals, public health organizations, etc., and appropriately subsidize the innovation of enterprises to enhance their innovation motivation.

Platelet-rich plasma attenuates intervertebral disc degeneration via delivering miR-141-3p-containing exosomes.

Oxidative stress mediated apoptotic and pyroptotic cell death contributes to intervertebral disc (IVD) degeneration, and platelet-rich plasma (PRP) exerts protective effects to attenuate IVD degeneration. Hence, the present study aimed to validate this issue and uncover the potential underlying mechanisms. The mice and cellular models for IVD degeneration were established by using puncture method and H2O2 exposure, respectively, and we evidenced that NLRP3-mediated cell pyroptosis, apoptosis and inflammatory responses occurred during IVD degeneration progression in vitro and in vivo. Then, the PRP-derived exosomes (PRP-exo) were isolated and purified, and we noticed that both PRP-exo and ROS scavenger (NAC) reversed the detrimental effects of H2O2 treatment on the nucleus pulposus (NP) cells. Further results supported that PRP-exo exerted its protective effects on H2O2 treated NP cells by modulating the Keap1-Nrf2 pathway. Mechanistically, PRP-exo downregulated Keap1, resulting in the release of Nrf2 from the Keap1-Nrf2 complex, which further translocated from cytoplasm to nucleus to achieve its anti-oxidant biological functions, and H2O2 treated NP cells with Nrf2-deficiency did not respond to PRP-exo treatment. In addition, miR-141-3p was enriched in PRP-exo, and miR-141-3p targeted the 3' untranslated region (3'UTR) of Keap1 mRNA for its degradation, leading to Nrf2 translocation. Furthermore, overexpression of miR-141-3p ameliorated the cytotoxic effects of H2O2 on NP cells, which were abrogated by upregulating Keap1 and silencing Nrf2. Taken together, we concluded that PRP secreted exosomal miR-141-3p to activate the Keap1-Nrf2 pathway, which helped to slow down IVD degeneration.

Inhibiting autophagy promotes endoplasmic reticulum stress and the ROS­induced nod­like receptor 3­dependent proinflammatory response in HepG2 cells.

Inflammation and endoplasmic reticulum (ER) stress are key contributors to insulin resistance and metabolic disease, and interleukin (IL)­1ß is involved in insulin resistance. The present study aimed to investigated the role of autophagy in LPS­induced ER stress and inflammation, which may provide evidence for controlling metabolic disease associated with inflammation. Lipopolysaccharide (LPS) induced the activation of ER stress and the nod­like receptor 3­dependent expression of IL­1ß and caspase­1, as shown by western blotting, which contributed to HepG2 cell death. This also involved the generation of mitochondrial reactive oxygen species and the autophagy signaling response, which are derived from the ER stress pathway. The percentage of apoptotic cells was measured by flow cytometry with fluorescein isothiocyanate/propidium iodide staining. Reactive oxygen species formation was detected by flow cytometry using the peroxide sensitive fluorescent probe 2',7'­dichlorofluorescin diacetate. Autophagy activation was measured by western blotting and confirmed using transmission electron microscopy. Furthermore, inhibiting autophagy promoted ER stress and the proinflammatory response in addition to cell death. These findings provide insights into the protective role of autophagy in LPS­induced cell death and ER stress, and further identified the association of autophagy, ER stress and inflammation in HepG2 cells.

Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes

Autophagy is a kind of cell biological process that maintains the cell’s energy level under nutrient-poor conditions, regulates the turnover of abnormal or aged proteins, and disposes of dysfunctional organelles. The autophagy system is activated as a novel signaling pathway in response to endoplasmic reticulum stress (ER stress)-induced insulin resistance (IR). Defective autophagy may be closely related to insulin resistance. There are at least three mechanistically distinct arms of ER stress that regulate the expression of key genes which not only function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids, and lipids. ER stress-stimulated insulin resistance is mediated by the autophagy-dependent process. In settings of chronic ER stress, the associated autophagy may contribute to pathophysiological processes involved in a number of prevalent diseases, including diabetes. Whether autophagy plays a protective or harmful role in diabetes awaits further analysis. In this review, we will summarize the current knowledge about the emerging role of autophagy in ER stress-induced insulin resistance. Strategies to take advantage of the potential protective effect of autophagy remain important in the overall treatment of insulin resistance and type 2 diabetes

Study of autophagy-related protein light chain 3 (LC3)-II expression levels in thyroid diseases.

Thyroid cancers are the most common malignant tumors of the endocrine system. The survival-promoting role of autophagy in tumor cells has been received universally. This study aimed to explore autophagy-related protein light chain 3 (LC3)-II expression levels in thyroid diseases including papillary thyroid cancer. A total of 45 thyroid samples, including 19 samples of papillary thyroid cancer, 7 samples of nodular goiter, 8 samples of Hashimoto thyroiditis and 11 samples of normal thyroid tissue resected during surgery, were selected and divided into pathological groups using light microscope. Levels of autophagy-related protein LC3-II in four different types of thyroid tissue were tested through Western blot. SPSS19 software was utilized to analyze the research data statistically. LC3-II protein levels in papillary thyroid cancer tissues were lower than that in normal thyroid tissues significantly (P<0.05). Compared with normal thyroid tissue, expression levels of LC3-II protein were higher in samples of Hashimoto thyroiditis and nodular goiter (P<0.05). Multi-factor analysis of variance showed that there was no significant correlation between LC3-II protein levels and patients' gender of thyroid cancer, while there was significant variation between patients with and without lymph node metastasis. Compared with patients of thyroid cancer without lymph node metastasis, the level of LC3-II protein was lower in patients of thyroid cancer with lymph node metastasis (P<0.05). Detection of LC3-II protein expression levels in thyroid diseases may contribute to the clinical diagnosis and provide theoretic basis for the therapy.

Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes.

Autophagy is a kind of cell biological process that maintains the cell's energy level under nutrient-poor conditions, regulates the turnover of abnormal or aged proteins, and disposes of dysfunctional organelles. The autophagy system is activated as a novel signaling pathway in response to endoplasmic reticulum stress (ER stress)-induced insulin resistance (IR). Defective autophagy may be closely related to insulin resistance. There are at least three mechanistically distinct arms of ER stress that regulate the expression of key genes which not only function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids, and lipids. ER stress-stimulated insulin resistance is mediated by the autophagy-dependent process. In settings of chronic ER stress, the associated autophagy may contribute to pathophysiological processes involved in a number of prevalent diseases, including diabetes. Whether autophagy plays a protective or harmful role in diabetes awaits further analysis. In this review, we will summarize the current knowledge about the emerging role of autophagy in ER stress-induced insulin resistance. Strategies to take advantage of the potential protective effect of autophagy remain important in the overall treatment of insulin resistance and type 2 diabetes.

Matrix metalloproteinase-1 (MMP1) polymorphism is associated with lowered risk of nasopharyngeal carcinoma in Asian population.

Data on the association between -1607 1G > 2G polymorphism in the promoter region of matrix metalloproteinase-1 (MMP1) and nasopharyngeal carcinoma (NPC) are conflicting. The aim of this study was to confirm whether this polymorphism was a causative factor of NPC. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) for studies on the present topic. A total of four publications (1,044 NPC patients and 1,284 healthy control subjects) were included and meta-analysis was performed to assess the association between -1607 1G > 2G polymorphism and NPC risk. Odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated for 1G1G versus 2G2G, 1G1G + 1G2G versus 2G2G, 1G1G versus 1G2G + 2G2G, 1G versus 2G, and 1G2G versus 2G2G contrast models. Meta-analysis results showed significantly reduced risk of NPC associated with the 1G1G versus 2G2G, 1G versus 2G and 1G2G versus 2G2G contrast models (OR = 0.61, 95 % CI 0.49-0.77; OR = 0.78, 95 % CI 0.65-0.92; OR = 0.86, 95 % CI 0.74-0.99, respectively). When we continued to perform subgroup analysis by ethnicity, the significant association persisted in Asian population and was most pronounced under the 1G2G versus 2G2G model (OR = 0.85, 95 % CI 0.73-0.99). These data suggested that MMP1 -1607 1G > 2G polymorphism was associated with reduced risk of NPC, particularly in the population of Asian descent.

Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes.

Type 2 diabetes is a chronic inflammatory disease. A number of studies have clearly demonstrated that cytokines such as interleukin 1ß (IL1ß) contribute to pancreatic inflammation, leading to impaired glucose homeostasis and diabetic disease. There are findings which suggest that islet ß-cells can secrete cytokines and cause inflammatory responses. In this process, thioredoxin-interacting protein (TXNIP) is induced by endoplasmic reticulum (ER) stress, which further demonstrates a potential role for ER stress in innate immunity via activation of the NOD-like receptor (NLRP) 3/caspase1 inflammasome and in diabetes pathogenesis via the release of cytokines. Recent developments have also revealed a crucial role for the autophagy pathway during ER stress and inflammation. Autophagy is an intracellular catabolic system that not only plays a crucial role in maintaining the normal islet architecture and intracellular insulin content but also represents a form of programmed cell death. In this review, we focus on the roles of autophagy, inflammation, and ER stress in type 2 diabetes but, above all, on the connections among these factors.

Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.

BACKGROUND: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells). METHODS: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation. RESULTS: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone. CONCLUSIONS: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.

Autophagy regulates inflammation following oxidative injury in diabetes.

T1D (type 1 diabetes) is an autoimmune disease characterized by lymphocytic infiltration, or inflammation in pancreatic islets called 'insulitis.' Comparatively speaking, T2D (type 2 diabetes) is traditionally characterized by insulin resistance and islet ß cell dysfunction; however, a number of studies have clearly demonstrated that chronic tissue inflammation is a key contributing factor to T2D. The NLR (Nod-like receptor) family of innate immune cell sensors such as the NLRP3 inflammasome are implicated in leading to CASP1 activation and subsequent IL1B (interleukin 1, ß) and IL18 secretion in T2D. Recent developments reveal a crucial role for the autophagy pathway under conditions of oxidative stress and inflammation. Increasingly, research on autophagy has begun to focus on its role in interacting with inflammatory processes, and thereby how it potentially affects the outcome of disease progression. In this review, we explore the pathophysiological pathways associated with oxidative stress and inflammation in T2D. We also explore how autophagy influences glucose homeostasis by modulating the inflammatory response. We will provide here a perspective on the current research between autophagy, inflammation and T2D.