Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.

OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis. METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting. RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC. CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

Association between optic atrophy 1 polymorphisms and primary open angle glaucoma risk: Based on a meta-analysis.

BACKGROUND: Emerging evidence suggested a significant association between optic atrophy 1 (OPA1) polymorphisms and primary open angle glaucoma (POAG) risk. However, the current data are inconsistent or even contradictory. Given these, we conducted a meta-analysis to examine the precise association between OPA1 polymorphisms and POAG risk. MATERIALS AND METHODS: Online databases were retrieved, and the related studies were reviewed from inception to December 1, 2022. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of each genetic model. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. RESULT: Overall, 14 studies within 11 publications (involving 2,413 POAG patients and 1,904 controls) were included and some significant association between OPA1 rs166850 C/T (T vs. C: OR = 1.24, 95%CI = 1.06-1.45, P = 0.01, I2 = 39.0%; CT vs. CC: OR = 1.37, 95%CI = 1.05-1.79, P = 0.02, I2 = 41.6%; CT + TT vs. CC: 1.37, 95%CI = 1.06-1.77, P = 0.02, I2 = 41.6%), rs10451941T/C (TC + CC vs. TT: OR = 1.79, 95%CI = 1.41-2.28, P < 0.01, I2 = 71.9%) polymorphisms and POAG susceptibility. In addition, further significant associations were also observed in the stratified analysis, especially in normal tension glaucoma groups and Caucasian descendants. CONCLUSION: The observed evidences suggest that OPA1 polymorphisms may be associate with POAG susceptibility significantly.

HLA-DPA1 overexpression inhibits cancer progression, reduces resistance to cisplatin, and correlates with increased immune infiltration in lung adenocarcinoma.

PURPOSE: Human Leukocyte Antigen-DP alpha 1 (HLA-DPA1) is a critical gene in antigen-presenting cells and plays a significant role in immune regulation. The objective of this study was to comprehensively analyze the roles of HLA-DPA1 and its association with lung adenocarcinoma (LUAD). METHODS: We utilized bioinformatics and conducted a meta-analysis to examine the roles of HLA-DPA1 expression on the progression and immunity of LUAD. We also performed CCK-8, wound healing, and Transwell assays to validate the functions of HLA-DPA1 in LUAD. RESULTS: HLA-DPA1 expression is downregulated in LUAD tissues and is associated with gender, race, age, smoking history, clinical stage, histological type, lymph node metastasis, and prognosis of patients with LUAD. HLA-DPA1 is involved in immune responses, leukocyte cell-cell adhesion, and antigen processing and presentation. Overexpression of HLA-DPA1 inhibits cancer cell proliferation, migration, and invasion while promoting cell sensitivity to cisplatin in A549 and A549/DDP cells. Additionally, overexpression of HLA-DPA1 correlates with tumor purity, stromal, immune, and ESTIMATE scores, the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils), and immune cell markers (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, and cluster of differentiation 8A). CONCLUSIONS: Decreased HLA-DPA1 expression is associated with poor prognosis and immune infiltration in LUAD while HLA-DPA1 overexpression inhibits cancer cell proliferation and progression. Therefore, HLA-DPA1 shows potential as a prognostic biomarker and a therapeutic target for LUAD.

The Clinical Effect and Mechanism of Prostant on Urinary Retention and Anal Pain.

Anal pain and urinary retention are the two most outstanding complications of the procedure for prolapse and hemorrhoids (PPH) surgery. This study intended to assess the clinical effect and mechanism of Prostant on urinary retention and anal pain after the PPH. Here, 30 patients received PPH surgery. The role and mechanism of Prostant in patients and mice with urinary retention and anal pain were evaluated. ANOVA tests were executed and differences between groups were regarded as statistically significant when p < 0.05. Prostant effectively improved the urination status, lower abdomen symptoms, time to urinate and score of VAS, and the reduction of TNF-α and IL-6. Similarly, Prostant can ameliorate the outcome of urodynamics in urinary retention mice. Mechanically, Prostant reversed the urinary retention-elevated the serum level of hs-CRP and TNF-α, reduction of IL-2, imbalance of Treg/Th17, and level of JAK2 and phosphorylated STAT3. Besides, Prostant ameliorated the pain as shown by the reduction of writhing response, and the elevation of threshold of pain and degree of swelling. Moreover, Prostant antagonized the pain-induced dysregulation of Treg/Th17. Therefore, Prostant can treat patients and mice with anal pain and urinary retention by modulating the balance of Th17/Treg to regulate the secretion and production of inflammatory factors. We hope our results can establish a scientific treatment approach for solving anal pain and urinary retention after PPH surgery of mixed hemorrhoids.

[Microscope assisted anterior cervical discectomy and fusion for the treatment of single segment cervical spondylotic myelopathy].

OBJECTIVE: To compare the efficacy of microscope assisted anterior cervical discectomy and fusion with conventional surgical approach in the treatment of single-segment cervical spondylotic myelopathy. METHODS: The clinical data of 89 patients with single-segment cervical spondylotic myelopathy treated from March 2015 to March 2019 were retrospectively analyzed. There were 55 males and 34 females, with an average of (52.00±11.36) years old. Among the patients, 34 cases were treated with conventional anterior cervical discectomy with fusion (conventional group), including C3,4 in 3 cases, C4,5 in 10 cases, C5,6 in 15 cases, C6,7 in 6 cases; 55 cases were treated with microscopeassisted anterior cervical discectomy with fusion (microscope group), including C3,4 in 5 cases, C4,5 in 23 cases, C5,6 in 20 cases, C6,7 in 7 cases. Operative time, intraoperative blood loss, hospital stay and complications were compared between two groups. Clinical efficacy was assessed by visual analogue scale(VAS), Japanese Orthopaedics Association (JOA) scores, Oswestry Disability Index(ODI) during follow-up period (postoperative 1 week, 3 months and 12 months). RESULTS: Intraoperative blood loss and hospital stay in microscope group were less than those in conventional group (P<0.05), and operative time of conventional group was shorter than that of microscope group (P<0.05). Postoperative JOA, VAS and ODI were significantly improved in each groups (P<0.05). VAS scores of microscope group were better than that of conventional group at 1 week and 3 months after operation(P<0.05), but there was no statistically significant difference between two groups at 12 months after operation (P>0.05). JOA scores of microscope group at each postoperative follow-up were better than that of conventional group (P<0.05). ODI scores of microscope group at 3, 12 months after operation were better than that of conventional group (P<0.05). CONCLUSION: Both methods can achieve satisfactory effect in treating single-segment cervical spondylotic myelopathy. However, microscope-assisted anterior cervical discectomy and fusion has advantages of clear vision, less bleeding and fewer intraoperative complications.

Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling.

Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor ß1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.