Nanotherapeutics targeting autophagy regulation for improved cancer therapy.

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

Nanomaterial-mediated modulation of the cGAS-STING signaling pathway for enhanced cancer immunotherapy.

Despite the current promise of immunotherapy, many cancer patients still suffer from challenges such as poor immune response rates, resulting in unsatisfactory clinical efficacy of existing therapies. There is an urgent need to combine emerging biomedical discoveries and innovations in traditional therapies. Modulation of the cGAS-STING signalling pathway represents an important innate immunotherapy pathway that serves as a crucial DNA sensing mechanism in innate immunity and viral defense. It has attracted increasing attention as an emerging target for cancer therapy. The recent advancements in nanotechnology have led to the significant utilization of nanomaterials in cancer immunotherapy, owing to their exceptional physicochemical properties such as large specific surface area and efficient permeability. Given the rapid development of cancer immunotherapy driven by the cGAS-STING activation, this study reviews the latest research progress in employing nanomaterials to modulate this signaling pathway. Based on the introduction of the main activation mechanisms of cGAS-STING pathway, this review focuses on nanomaterials that mediate the agonists involved and effectively activate this signaling pathway. In addition, combination nanotherapeutics based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as other immunomodulation in tumor targeting therapy. STATEMENT OF SIGNIFICANCE: Given the rapid development of cancer immunotherapy driven by the cGAS / STING activation, this study reviews the latest research advances in the use of nanomaterials to modulate this signaling pathway. Based on the introduction of key cGAS-STING components and their activation mechanisms, this review focuses on nanomaterials that can mediate the corresponding agonists and effectively activate this signaling pathway. In addition, combination nanotherapies based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as immunomodulation in cancer therapy,.

The relationship between serum homocysteine levels and sudden sensorineural hearing loss: a meta-analysis.

OBJECTIVE: There was disagreement over the association between serum/plasma homocysteine (HCY) levels and sudden sensorineural hearing loss (SSNHL). Through the use of a meta-analysis, this study aims to determine whether there is a significant difference in serum homocysteine levels between the SSNHL group and the control group. DESIGN: The Cochrane Library, EMBASE, and PubMed databases were all thoroughly searched. The two independent reviewers thoroughly examined the initially searched articles. The data results were calculated by standard mean difference (SMD) or odds ratios (OR). Review Manager (version 5.3) was applied to statistical data. STUDY SAMPLE: There were 766 participants in the 6 trials with continuous outcomes that were part of the meta-analysis A. In addition, meta-analysis B, which included 961 people, contained a total of 3 studies with dichotomous results. RESULTS: Both meta-analyses revealed the same conclusion that serum/plasma HCY levels in the SSNHL patients are higher than those in the controls (SMD 0.41, 95 % confidence interval (CI) 0.11 to 0.72, P < 0.01; OR 3.27, 95 % CI 2.16 to 4.94, P < 0.01). CONCLUSION: This study demonstrated that the SSNHL patients' serum/plasma HCY levels were greater than those of the control group.

The differences in plasma/serum ghrelin levels between obstructive sleep apnea-hypopnea patients and controls: A protocol for systematic review and meta-analysis.

BACKGROUND: The association between obstructive sleep apnea-hypopnea syndrome (OSAHS) and plasma/serum ghrelin levels remains controversial. We performed a meta-analysis to evaluate the difference in plasma/serum ghrelin levels between OSAHS patients and controls. METHODS: Database of PubMed, SCI, and Elsevier were searched entirely. Two independents identified eligible studies of ghrelin levels in OSAHS patients. ReviewManager (version 5.3) was adopted for data synthesis. RESULTS: The meta-analysis A pooled the comparison of ghrelin concentrations in OSAHS patients and controls, which included 7 studies and involving 446 participants. The result of the meta-analysis A indicated that plasma/serum ghrelin levels were no significant differences between the OSAHS group and the control group (standard mean difference (SMD) = 0.08, 95% confidence interval (CI) = -0.12 to 0.28, P = .43). As a supplementary, meta-analysis B pooled the comparison of plasma/serum ghrelin levels in OSAHS patients before and after continuous positive airway pressure (CPAP) therapy, which included 155 participants from 4 studies, it revealed that plasma/serum ghrelin levels were no significant differences between before and after CPAP therapy (SMD = 0.12, 95%CI = -0.07 to 0.31, P = .22). CONCLUSION: The meta-analysis A demonstrated that plasma/serum ghrelin levels were no significant differences between the OSAHS group and the control group. The meta-analysis B showed plasma/serum ghrelin levels have no significant changes after CPAP therapy in OSAHS patients.

Prostatic-specific antigen (PSA) levels in patients with polycystic ovary syndrome (PCOS): a meta-analysis.

PURPOSE: The polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder, clinically characterized by oligo-ovulation/chronic anovulation, menstrual irregularities, hyperandrogenism (such as hirsutism, acne), hyperinsulinemia, and obesity. Prostatic-specific antigen (PSA) has been identified as a potential new marker in PCOS women. Although the precise role of PSA in PCOS patients still remains undetermined, PSA might serve as a useful clinical marker and might even represent a new diagnostic criterion of hyperandrogenemia in females of PCOS. METHODS: A meta-analysis was performed in the study to identify the association between the polycystic ovary syndrome and prostatic-specific antigen. To identify eligible original articles, we searched a range of computerized databases, including Medline via PubMed, EMBASE, CNKI and Web of Science with a systematic searching strategy. The characteristics of each study and standard mean differences (SMD) with corresponding confidence intervals (CIs) were calculated and subgroup analysis was performed to analyze heterogeneity. RESULTS: A total of 532 patients from seven articles were included in the meta-analysis. We identified a significant relationship between polycystic ovary syndrome and prostatic-specific antigen, with a pooled SMD of 0.81 (95% CI: 0.58 to 1.04; P < 0.01). The pooled data were calculated with the random-effects model as a moderate significant heterogeneity was found among the studies. CONCLUSIONS: The meta-analysis suggested that there was a significant association between the polycystic ovary syndrome and prostatic-specific antigen and we should not ignore the role of PSA in the PCOS patients in clinical.

The relationship between obstructive sleep apnea hypopnea syndrome and gastroesophageal reflux disease: a meta-analysis.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) means apnea and hypopnea caused by partial or complete obstruction of upper airway collapse during sleep. Gastroesophageal reflux disease (GERD) is believed to be associated with various manifestations in the otorhinolaryngology and has been found to be an additional risk factor for OSAHS. AIM: A meta-analysis was performed to identify the association between obstructive sleep apnea hypopnea syndrome and gastroesophageal reflux disease. METHODS: To identify eligible original articles, we searched a series of computerized databases, including Medline via PubMed, EMBASE, Web of Science, and CNKI with a systematic searching strategy. The characteristics of each article and pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated and subgroup analysis was performed to analyze the source of heterogeneity. RESULTS: A total of 2699 patients from seven articles were included in the meta-analysis. We identified a significant relationship between obstructive sleep apnea syndrome and gastroesophageal reflux disease, with a pooled OR of 1.75 (95% CI 1.18-2.59, P < 0.05). The pooled data was calculated under the random-effects model as a significant moderate heterogeneity was found among the meta-analysis. CONCLUSIONS: The meta-analysis showed that there was a significant correlation between obstructive sleep apnea hypopnea syndrome and gastroesophageal reflux disease.

The relationship between adenoid hypertrophy and gastroesophageal reflux disease: A meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is believed to be associated with various manifestations in the otorhinolaryngology and has been found to be an additional risk factor for adenoid hypertrophy, but the causal relation between them is under controversial. We thus performed a meta-analysis to grade the strength of evidence and systematically explore whether adenoid hypertrophy correlates with GERD in the literature. METHODS: A systematic literature search was performed using Medline via PubMed, Embase, CNKI, and Web of Science. Studies reporting the adenoid hypertrophy and GERD were identified for inclusion. RESULTS: There were 6 studies that matched the selection criteria, and the total sample size of these studies was 548 cases. We identified a significant relationship between adenoid hypertrophy and GERD, with a pooled odds ratio of 4.12 (95% confidence interval [CI]: 1.32-12.93; P < .001). The results was significant in 24-hour pH monitoring subgroup analysis, with a corresponding value of 8.62 (95% CI: 4.06-18.27, P > .05) under the fixed-effects model. And the results was significant in Helicobacter pylori subgroup analysis, with a corresponding value of 2.39 (95% CI: 0.39-14.55, P < .05) under the random-effects model. Begg tests (P = .73) and Egger tests (P = .76) showed there were no obvious evidence to support publication bias in our study. CONCLUSION: This meta-analysis provided a strong correlation between adenoid hypertrophy and GERD, the children with adenoid hypertrophy had a higher incidence of GERD than healthy children, but the pathogenesis of GERD in adenoid hypertrophy awaits more investigations and suggests that we should not overlook GERD in clinical practice and an appropriate evaluation for GERD may be needed.

Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis.

BACKGROUND: The death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ-induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC). However, the results of these studies are inconsistent. Hence, the present study aimed to evaluate the association between the promoter methylation of DAPK gene and HNSCC. METHODS: Relevant studies were systematically searched in PubMed, Web of Science, Ovid, and Embase. The association between DAPK promoter methylation and HNSCC was assessed by odds ratio (ORs) and 95% confidence intervals (CI). To evaluate the potential sources of heterogeneity, we conducted the meta-regression analysis and subgroup analysis. RESULTS: Eighteen studies were finally included in the meta-analysis. The frequency of DAPK promoter methylation in patients with HNSCC was 4.09-fold higher than the non-cancerous controls (OR = 3.96, 95%CI = 2.26-6.95). A significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region (Asian region, OR = 4.43, 95% CI = 2.29-8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18-9.78). In the control source, the significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group (autologous group, OR = 2.71, 95% CI = 1.49-4.93; heterogeneous group, OR = 9.50, 95% CI = 2.98-30.27). DAPK promoter methylation was significantly correlated with alcohol status (OR = 1.85, 95% CI = 1.07-3.21). CONCLUSION: The results of this meta-analysis suggested that aberrant methylation of DAPK promoter was associated with HNSCC.

Aberrant Methylation of MGMT Promoter in HNSCC: A Meta-Analysis.

BACKGROUND: O6-methylguanine-DNA methyl-transferase (MGMT) gene, a DNA repair gene, plays a critical role in the repair of alkylated DNA adducts that form following exposure to genotoxic agents. MGMT is generally expressed in various tumors, and its function is frequently lost because of hypermethylation in the promoter. The promoter methylation of MGMT has been extensively investigated in head and neck squamous cell carcinoma (HNSCC). However, the association between the promoter methylation of MGMT and HNSCC risk remains inconclusive and inconsistent. Therefore, we performed a meta-analysis to better clarify the association between the promoter methylation of MGMT and HNSCC risk. METHODS: A systematical search was conducted in PubMed, Web of Science, EMBASE, and Ovid for studies on the association between MGMT promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (CI) were calculated to estimate association between MGMT promoter methylation and risk of HNSCC. The meta-regression and subgroup analysis were undertaken to explore the potential sources of heterogeneity. RESULTS: Twenty studies with 1,030 cases and 775 controls were finally included in this study. The frequency of MGMT promoter methylation was 46.70% in HNSCC group and 23.23% in the control group. The frequency of MGMT promoter methylation in HNSCC group was significantly higher than the control group (OR = 2.83, 95%CI = 2.25-3.56). CONCLUSION: This meta-analysis indicates that aberrant methylation of MGMT promoter was significantly associated with the risk of HNSCC, and it may be a potential molecular marker for monitoring the disease and may provide new insights to the treatment of HNSCC.

Association between P16INK4a Promoter Methylation and Ovarian Cancer: A Meta-Analysis of 12 Published Studies.

BACKGROUND: Ovarian cancer is the primary cause of death in women diagnosed with gynecological malignancies worldwide. Absence of early symptoms prevents prompt diagnosis or successful therapeutic intervention. P16INK4a is a well-known tumor suppressor gene (TSG). Aberrant methylation of TSG promoter is an important epigenetic silencing mechanism leading to ovarian cancer progression. Studies have reported differences in methylation frequencies of the p16INK4a promoter between ovarian cancer and the corresponding control group. However, the association between p16INK4a promoter methylation and ovarian cancer remains unclear and controversial. Therefore, a meta-analysis was conducted to clarify the relationship between p16INK4a promoter methylation and ovarian cancer. METHODS: PubMed, Web of Science, EMBASE and CNKI were searched to identify eligible studies for the evaluation of the association between p16INK4a promoter methylation and ovarian cancer. Odds ratio (ORs) and 95% confidence intervals (95%CI) were calculated to determine the strength of association between p16INK4a promoter methylation and ovarian cancer. RESULTS: A total of 612 ovarian cancer patients and 289 controls from 12 eligible studies were included in the meta-analysis. Overall, a significant association was observed between p16INK4a methylation status and ovarian cancer risk using a fixed-effects model (OR = 2.02, 95% CI = 1.39-2.94). CONCLUSION: The results of our meta-analysis show that aberrant methylation of p16INK4a promoter was significantly associated with ovarian cancer. It may represent a promising molecular marker to monitor the disease and provides new insights into the treatment of human ovarian cancer.