Promotion of Inflammation, Apoptosis, and Inhibition of Autophagy by Overexpression of lncRNA SNHG12 in Acute Kidney Injury.

\Introduction. There is a dispute regarding the roles of newly discovered lncRNAs in acute kidney injury (AKI). Therefore, this study discussed long non-coding RNA (lncRNA) small nuclear host gene 12 (SNHG12) in AKI and its molecular mechanism. METHODS: Lipopolysaccharide (LPS) induction was treated into renal tubular epithelial cells (HK-2 cells) to induce septic AKI in vitro. In the cell model, SNHG12, miR-1270, and tubulin beta class I (TUBB) expression patterns, along with p-p65, cleaved caspase-3, Beclin-1, p62, and autophagy related 7 (ATG7) protein expressions, were determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. Cell viability was evaluated by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) cytotoxicity assay, while apoptosis and inflammation were assessed by flow cytometry and enzymelinked immunosorbent assay (ELISA), respectively. At last, the mechanistic interaction between SNHG12, miR-1270, and TUBB was identified. RESULTS: SNHG12 was highly expressed in LPS-induced HK-2 cells. Functionally, knocking down SNHG12 increased cell viability and autophagy, while inhibited LDH release, inflammation, and apoptosis. Mechanically, SNHG12 absorbed miR-1270 to upregulate TUBB expression, thereby aggravating inflammation, apoptosis, and inhibiting autophagy in AKI. CONCLUSION: SNHG12 promotes inflammation, apoptosis, and autophagy by targeting the miR-1270/TUBB axis in AKI.  DOI: 10.52547/ijkd.7903.

Head and neck cancer with synchronous nodules of the lung as a diagnostic and therapeutic challenge - A systematic review.

Head and neck squamous cell carcinoma (HNSCC) often presents with synchronous nodules of the lung (sNL), which may be benign nodules, second primary malignancies or metastases of HNSCC. We sought to gain an insight into the incidence of sNL and synchronous second primary of the lung (sSPML) in HNSCC patients and current opinions on useful diagnostic and therapeutic approaches. We conducted a systematic search of the PubMed database for articles that reported the simultaneous detection of HNSCC and sNL/sPML, within the timeframe of diagnosis and staging. Only studies involving humans were included, without restrictions for sex, age, ethnicity, or smoking history. All articles were categorised according to the Oxford Centre of Evidence-Based Medicine levels and their data collected. Data from 24 studies were analysed. Amongst HNSCC, the mean overall incidence rate of sNL and sSPML was 11.4% (range: 1.3-27%) and 2.95% (range: 0.4-7.4%), respectively. The possibility of a sNL to be a sSPML cannot be ignored (mean: 35.2%). Studies investigating smoking habits showed that the majority (98-100%) of HNSCC patients with sSPML were previous or active smokers. Detection of human papillomavirus through DNA analysis, p16 immunohistochemistry, and identification of clonal evolution were useful in differentiating metastasis from sSPML. 18FDG-PET scan was the most reliable method to diagnose sSPML (sensitivity: 95%; specificity: 96%; positive predictive value: 80%). With early sSPML detection and curative treatment, the 5-year overall survival rate is 34-47%. However, the proposed advantage of early detection warrants further evidence-based justification.

The effects of wine-processing on ascending and descending: The distribution of flavonoids in rat tissues after oral administration of crude and wine-processed Radix scutellariae.

ETHNOPHARMACOLOGICAL RELEVANCE: Ascending and descending theory is a core principle of traditional Chinese medicine (TCM) theories. It plays an essential role in TCM clinical applications. Some TCM medicine has specific properties, which could alter the inclination and direction of their actions. The properties of the ascending and floating process of one herbal medicine are affected by means of herb processing. Wine-processing, which is sautéing with rice wine, is one of the most popular technologies of herb processing. Wine-processing increases the inclination and direction of its actions, thereby producing or strengthening their efficacy in cleaning the upper-energizer heat. Radix scutellariae, the dried roots of Scutellaria baicalensis Georgi, is a well-known TCM used for the treatment of inflammation, pyrexia, jaundice, etc. Recently, wine-processed Radix scutellariae was normally applied in clinical studies for the treatment of upper-energizer syndrome. In order to investigate the effects of wine-processing on ascending and descending of Radix scutellariae, the comparative study of distribution of flavonoids in rat tissues of triple energizers (SanJiao-upper, middle, lower jiao) after oral administration of crude and wine-processed Radix scutellariae aqueous extracts was carried out. MATERIALS AND METHODS: The rats were randomly assigned to two groups and orally administered with crude and wine-processed Radix scutellariae aqueous extracts, respectively. At different pre-determined time points after administration, the concentrations of compounds in rat tissue homogenate were determined, and the main tissue pharmacokinetic parameters were investigated. Tissue pharmacokinetic parameters including AUC0-t, t1/2, Tmax and Cmax were calculated using DAS 2.0. An unpaired Student t-test was used to compare the differences in tissue pharmacokinetic parameters between the two groups. All the results were expressed as arithmetic mean±S.D. RESULTS: The parameters of Cmax and AUC0-t of some flavonoids in wine-processed Radix scutellariae were remarkably increased (p<0.05, p<0.01, p<0.001) in the rat upper-energizer tissues (lung and heart) compared with those of the crude group. However, in the rat middle- and lower-energizer tissues (spleen, liver and kidney), the Cmax and AUC0-t of some flavonoids were significantly decreased (p<0.05, p<0.01) compared with the crude group. The main explanation for these differences seems to the effects of wine-processing on ascending and descending theory. CONCLUSIONS: All of these differences in the distribution of triple energizers after oral administration of crude and wine-processed Radix scutellariae aqueous extracts may lead to the increase of efficacy on the upper-energizer tissues and were in compliance with the ascending and descending theory. Therefore, wine-processing was recommended when Radix scutellariae was used for cleaning the upper-energizer heat and humidity. The obtained knowledge can be used to evaluate the impact of these differences on the efficacy of both the drugs in clinical applications and might be helpful in explaining the effects of wine-processing on ascending and descending theory.

High glucose decreases collagenase expression and increases TIMP expression in cultured human peritoneal mesothelial cells.

BACKGROUND: Peritoneal fibrosis (PF), a serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, is characterized by extracellular matrix (ECM) accumulation which results from an imbalance between the synthesis and the degradation of ECM components. Previous studies have demonstrated that ECM synthesis is increased in human peritoneal mesothelial cells (HPMCs) under high glucose conditions, but the effects of high glucose on degradative pathways have not been fully explored. This study was undertaken to elucidate the effects of high glucose on these proteolytic processes in cultured HMPCs. METHODS: HPMCs were isolated from human omentum and were exposed to 5.6 mM glucose (NG), 5.6 mM glucose +34.4 mM mannitol (NG + M), or 40 mM glucose (HG) with or without PKC inhibitor (PKCi). Real-time PCR and western blot were performed to determine collagenases (MMP-1, -8 and -13) and TIMPs (TIMP-1 and -2) mRNA and protein expression, respectively. The individual activities of collagenases in culture media were determined by ELISA. RESULTS: Types I and III collagen protein expression were significantly increased in HG-conditioned media compared to NG media (P < 0.05). The MMP-1, -8 and -13/GAPDH mRNA ratios were significantly lower in HPMCs exposed to HG medium compared to NG cells by 64, 52 and 37%, respectively, and their protein expression by 76, 42 and 49%, respectively, in HG- vs NG-conditioned media. The activities of collagenases in HG-conditioned media were also significantly lower than those in NG media (P < 0.05). In contrast, HG significantly increased TIMPs mRNA ratios and protein expression in HPMCs. These changes in collagenase and TIMP expression induced by HG were abrogated upon pre-treatment with PKCi. CONCLUSION: In conclusion, impaired matrix degradation may contribute to ECM accumulation in PF.

Glomerular glucocorticoid receptor expression is reduced in late responders to steroids in adult-onset minimal change disease.

BACKGROUND: Compared to children, adult patients with minimal change disease (MCD) tend to have a slower response to steroids, but little is known about the factors influencing the steroid responsiveness in these patients. In this study, we investigated the difference in the expression of the glomerular glucocorticoid receptor (GCR) according to steroid responsiveness in 28 adult-onset MCD patients. METHODS: Based on the response to steroid treatment, the patients were divided into early responders (ER, n=20) and late responders (LR, n=8) according to the response to steroids on the basis of 4 weeks of treatment. The clinical and laboratory findings, and the glomerular mRNA and protein expression of GCR and nephrin, assessed by real-time polymerase chain reaction and immunohistochemistry, respectively, were compared between the ER and LR groups. Ten microscopic haematuric patients in whom renal biopsy was performed and revealed no histological abnormalities were included for control (C). RESULTS: The mRNA expression of GCR was significantly lower in the LR than that in the ER group (P<0.01), whereas it was comparable between the C and ER groups. GCR protein expression was also decreased in the LR compared with the C and ER groups. In contrast, there was no significant difference in nephrin mRNA expression among the three groups. On the other hand, the GCR mRNA expression correlated inversely with the time to complete remission (r= -0.49, P<0.05), but not with the amount of proteinuria at presentation. CONCLUSION: In conclusion, the levels of glomerular GCR expression may be a useful predictor of steroid responsiveness in adult-onset MCD patients.