BIOCELL

Lung Development: AT1 and AT2 Property

Yong chen — Mon, 11 May 2020 00:00:00 +0800

The human respiratory system consists of the upper respiratory and the lower respiratory. The lower respiratory includes the trachea, bronchi, bronchioles (terminal bronchioles and respiratory bronchioles), alveolar duct, alveolar duct sacs and alveoli. Alveoli are composed of two epithelial cell types, cuboidal alveolar type 2 (AT2) cells that secrete surfactant to prevent alveolar collapse and function as stem cells to regenerate alveolar type 1 (AT1) cells during damage repair, and squamous AT1 cells that cover most of the surface area of the alveoli and mediate gas exchange. This review summarizes the current studies on lung development, and property on AT1/ AT2 cells.

Role of pyroptotic cell death in the pathogenesis of NASH

Dan Weng, Yuguo Yi, Jiamin Zheng, Yang Zhou, Zhiqin Liu — Mon, 11 May 2020 00:00:00 +0800

Nonalcoholic fatty liver disease (NAFLD) represents a huge treat to public health of the whole world. Around 25% of NAFLD patients will progress to nonalcoholic steatohepatitis (NASH), which has been predicted to be the main reason for liver transplantation in US in 2020. Extensive effort has been devoted into investigating the underlying molecular mechanisms of NASH pathogenesis and developing new promising treatment. Recent studies have demonstrated that pyroptosis, an inflammatory programmed cell death mediated by inflammasome and gasdermin-D (GSDMD), is involved in the development and progression of NASH. This review aims to summarize the recent findings regarding the role of pyroptosis and related molecules in the pathogenesis of NASH.

Comparative characterization of human fetal neural stem cells and induced neural stem cells from peripheral blood mononuclear cells

yimin Fan — Mon, 11 May 2020 00:00:00 +0800

Human induced neural stem cells (iNSCs) transplantation is a potential treatment of neurodegeneration diseases, however, whether the reprogrammed cells have the same characterizations as human fetal neural stem cells needs further exploration. Here we isolated human fetal neural stem cells from aborted 12-weeks fetal brain and compared with iNSCs reprogrammed from human peripheral blood mononuclear cells in gene expression, proliferation ability, differentiation capacity, and the responses to tumor necrosis factor-α. We found that iNSCs and NSCs both expressed neural stem cells markers Nestin, SOX1 and SOX2. However, only iNSCs can be patterned into dopaminergnice neurons and motor neurons. Furthermore, both iNSCs and NSCs can differentiate into oligodendrocyte progenitor cells. In addition, low dose of tumor necrosis factor-α did not inhibit proliferation and differentiation of iNSCs and NSCs. In conclusion, iNSCs have properties similar and even better than fetal neural stem cells and may be suitable for disease modeling and transplantation.

An in vitro study to explore the role of Prolylcarboxypeptidase in non-small cell lung cancer.

Qian Bin Bin, Liu Xiaoduo, Gu Xiaolin, Yang Lu, Chen Dake — Mon, 11 May 2020 00:00:00 +0800

Prolylcarboxypeptidase (PRCP) belongs to S28 family of proteases, which is also a dipeptidyl peptididase.In this study we demonstrate the expression pattern of PRCP in Non-small cell lung cancer (NSCLC).We found that the repression of PRCP expression by small interfering RNA successfully inhibited cell proliferation, migration and invasion. Further we explored the involvement of PRCP in the regulation of epithelial-mesenchymal transition (EMT).The epithelial marker E-cadherin was significantly increased, meanwhile mesenchymal markers MUC1, Vimentin and SNAIL were markedly decreased in PRCP knockdown cells. Moreover the downregulation of PRCP in the NSCLC cells induced the expression of apoptosis-related proteins in vitro. We performed RT-PCR in 30 pairs of clinical NSCLC tissues and adjacent non-cancerous tissues which revealed, significantly higher PRCP expression levels in cancer tissues than in adjacent non-cancerous tissues. Collectively the results from our study suggest a possible cancer promotion role of PRCP in NSCLC.

Hesperetin administration and mesenchymal stem cell therapy ameliorate lipid profile, heart function, kidney function and antioxidant activity in STZ diabetic rats

Osama M. Ahmed, Mohamed A. Hassan, Dr., Ablaa S. Saleh — Mon, 11 May 2020 00:00:00 +0800

This study aimed to assess the effect of hesperetin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) on lipid profile, heart and kidney functions as well as cardiac and renal lipid peroxidation and antioxidant defense system in streptozotocin (STZ) diabetic rats. Type 1 diabetes mellitus (T1DM) was induced in male Wistar rats by injecting 40 mg/kg body weight (b.w.) STZ dissolved in citrate buffer (pH 4.5). The diabetic rats were treated with hesperetin orally administered at dose 20 mg/kg b.w., BM-MSCs intravenously injected at dose of 1 x10⁶ cells/rat/week and their combination for 6 weeks. The diabetic rats exhibited lipid abnormalities manifested by elevated serum levels of total cholesterol, triglycerides, LDL-cholesterol and vLDL-cholesterol and lowered HDL-cholesterol as well as elevated liver cholesterol and triglycerides content in association with the resultant fasting and post-prandial hyperglycemia and insulin deficiency. The heart function biomarkers including CK-MB, AST and LDH activities as well as levels of kidney function parameters, creatinine and urea, were significantly raised in serum of diabetic rats. These changes were concomitant with abnormal redox balance represented by elevated lipid peroxidation, decreased glutathione content and suppressed antioxidant enzyme activities in both heart and kidney of diabetic rats. The previous deleterious alterations were significantly ameliorated after the treatment of diabetic rats with hesperetin and BM-MSCs singly or in combination; the treatment with hesperetin together with BM-MSCs was the most potent. Based on these findings, it can be concluded that the use of hesperetin with MSCs may have more additive therapeutic value than their uses singly in T1DM. In addition, the ameliorative effects of hesperetin and BM-MSCs on lipid profile and heart and kidney functions in diabetic rats may be mediated, at least in part, via their suppressive effects on oxidative stress and ameliorative effects on the antioxidant defense system secondary to improvement in the hyperglycemia and insulin secretory response.

The Thyme oil and thymol abrogate doxorubicin-induced nephrotoxicity and cardiotoxicity in Wistar rats via repression of oxidative stress and enhancement of antioxidant defense mechanisms

Osama M. Ahmed, Sanaa R. GALALY, Mennah-Allah MOSTAFA — Mon, 11 May 2020 00:00:00 +0800

This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin (DOX)-induced renotoxicity, cardiotoxicity and oxidative stress in Wistar rats. Rats administered DOX at dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent, thymol, at doses 250 and 100 mg/kg b.w./every other day respectively for the same period. Thyme oil and thymol markedly ameliorated the kidney function marked by the decrease in the raised levels of serum urea, uric acid and creatinine as well as the heart function manifested by the decrease in the elevated activities of serum CK-MB and LDH in the thyme oil and thymol treated DOX-injected rats. Lipid peroxidation was significantly decreased while GSH level and GST and GPx activities were significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol. The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft, inflammatory cells infiltration, protein cast in lumina of the renal tubule and thickening of parietal layer of Bowman's capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol. In addition, DOX-induced deleterious heart histological alterations including intramuscular inflammatory cells infiltration, focal necrosis of cardiac myocytes and odema were remarkably amended by treatment with thyme oil and thymol. Thus, it can be concluded that DOX could induce marked toxicity in kidney and heart and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.

Significant association of a single nucleotide polymorphism in the upstream region of FGFR1OP2/wit3.0 gene with Residual Ridge Resorption of Mandible in Saudis

Narasimha Reddy Parine — Mon, 11 May 2020 00:00:00 +0800

Residual Ridge Resorption (RRR), is the slow decrease in the jaw structure which follows tooth extraction. It appears as a multifactorial disorder with both environmental and genetic factors playing a role in its etiology. Reports on the genetic factors associated with RRR are very scarce and only a couple of studies are reported on Saudi patients. The aim of this study was to investigate the role of single nucleotide polymorphisms (SNPs) in fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2), a factor implicated in the process of rapid wound healing that is known to occur in the oral cavity, in RRR development in Saudi patients.

Methods

The study included 96 patients suffering from RRR, attending outpatient clinics at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia, and an equal number of age and sex matched healthy controls attending outpatient clinics for minor illnesses. Demographic and relevant clinical data were collected, the digital panoramic dental radiograph (OPG) was obtained and mandibular residual ridge height was measured. Saliva samples were collected and used for extraction of DNA. Three SNPs were selected and genotyping was carried out using ‘Sequenom MassARRAY iPLEX’, following the methods recommended by the manufacturer. Genotypes were assigned based on the differences in their masses on MALDI-TOF mass spectrometer. Genotype and allele frequencies were calculated manually in the patients and control groups and compared. Odds ratio (OR), 95% confidence intervals (CI), Chi square (χ²) and p values were obtained. The age at first diagnosis and bone height were compared in the three genotypes of each SNP.

Results

The age of the patients ranged from 21-80 years, age at first edentulism ranged from 12 to 70 years and the bone height ranged from 13 mm to 34.6 mm. All three genotypes of the three studied SNPs (rs2279351, rs78054962 and rs2306852) were identified. rs2279351 associated significantly with RRR and the mutant C allele was highly predisposing. No association was observed for the other two alleles. The genotypes, of all SNPs, had an influence on age at first edentulism and bone height, but the results were not different statistically.

Conclusion

Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity, it may also be playing a role in the development of RRR by influencing the rate of resorption of the jaw bone. Polymorphism (rs2279351), may alter its expression and hence RRR development. Further studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.

Isolation and molecular identification of cellulolytic bacteria from hot spring and studying their cellulase activity

Mon, 11 May 2020 00:00:00 +0800

Cellulose is the main structural component of lignocellulosic wastes that can be converted to sugars and biofuels by cellulase. Due to wide applications of this enzyme in various industries around the world, cellulase is considered as the third industrial enzyme. The ability of thermophilic bacteria in production of heat-stable cellulases has made them valuable tools in biotechnology. The aim of this study was isolation and molecular identification of cellulolytic thermophile bacteria from Dig Rostam hot spring, situated close to Kerman, southeast of Iran, and investigating their cellulase activity. Samples were taken from water and sediments of this hot spring, and cellulolytic bacteria were enriched in media containing cellulose as the only carbon source. The bacteria were incubated at 60˚C and single colonies were then isolated on solid media. Congo red assay was used as a quick test for qualitative screening of cellulase activity. According to these qualitative results 4 colonies named CDB1, CDB2, CDB3 and CDB4 were isolated and their endoglucanase, exoglucanase and FPase activities were investigated quantitatively. Results indicated that CDB1 exhibited the highest endoglucanase (0.096 U/ml) and exoglucanase (0.156 U/ml) activities among other isolates. 16S rDNA partial sequencing indicated that CDB1 had %99 similarity to Anoxybacillus genus and the other isolates showed the highest similarity to Geobacillus genus. Moreover, growth curve and some other characteristics of the isolated bacteria were also determined by biochemical assays. The cellulase gene of CDB1 isolate with the highest cellulase activity was also cloned and its sequence is reported for the first time. Further studies on this thermophilic enzyme might be useful for industrial applications.

MicroRNA-708 inhibits the proliferation and chemoresistance of pancreatic cancer cells

donglin sun — Mon, 11 May 2020 00:00:00 +0800

Pancreatic cancer is one of the most aggressive malignancies with poor prognosis and high mortality. Recent studies showed that microRNAs (miRNAs) are dysregulated and involved in the initiation and progression of pancreatic cancer. In this study, we found that miR-708 was significantly downregulated in pancreatic cancer tissues and cell lines. Lentivirus-mediated overexpression of miR-708 could significantly inhibit the proliferation and invasion, while enhance chemosensitivity to gemcitabine in both Panc-1 and SW1990 cells. Luciferase reporter assay showed that miR-708 bound the 3'-untranslated region of survivin, and suppressed the expression of survivin in pancreatic cancer cells. In pancreatic cancer tissues, survivin protein was highly expressed and negatively correlated with miR-708 expression. Furthermore, the restoration of survivin expression could partially antagonize proliferation inhibition and apoptosis induction by miR-708 in pancreatic cancer cells. The Panc-1 cells with overexpression of miR-708 also showed decreased proliferation capability in nude mouse model, compared with parental cells. In conclusion, our results suggest that miR-708 inhibits pancreatic cancer and could be a novel potential candidate to treat pancreatic cancer.

Effect of MicorRNA-143-3p-mediated CTNND1 on the Biological Function of Lung Cancer Cells

Zhongjun Jiang, Xinxiong Fei, Wenbin Hu, Gangsheng Wang, Chunyan Su, Xuqun Huang — Mon, 11 May 2020 00:00:00 +0800

AIM: To investigate the effect of miR-143-3p-mediated CTNND1 on the proliferation, invasion, and apoptosis of lung cancer cells. METHODS: Eighty-seven samples of lung cancer tissues and 81 samples of tumor-adjacent tissues from patients undergoing radical lung cancer surgery in our hospital were collected. The lung cancer cells and lung fibroblast cells (HFL-1) were purchased, and then mir-143-3p-mimics, miR- NC, si-CTNND1, NC were transfected into A549, PC-9 cells. qRT-PCR was used to measure the expression of mir-143-3p and CTNND1 in lung cancer tissues and cells, and Western Blot (WB) was employed to detect the expression of Bax, Bcl-2, and CTNND1. MTT assay, Transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis. Dual luciferase report assay was used to determine the relationship between mir-143-3p and CTNND1. RESULT: miR-143-3p was lowly expressed in lung cancer and CTNND1 was highly expressed in lung cancer. The overexpression of miR-143-3p inhibited cell proliferation and invasion, promoted cell apoptosis, significantly increased Bax protein expression, and decreased Bcl-2 protein expression. The inhibition of miR-143-3p inhibited cell proliferation and invasion, promoted cell apoptosis, significantly increased Bax protein expression, and decreased Bcl-2 protein expression. The dual luciferase reporter assay demonstrated that miR-143-3p was a target region of CTNND1. CONCLUSION: miR-143-3p can inhibit the proliferation and invasion of lung cancer cells by regulating the expression of CTNND1, and promote the apoptosis of lung cancer cells. It is expected to be a potential target for lung cancer.

Cell viability in the cadmium–stressed cell suspension cultures of tobacco is regulated by extracellular ATP possibly by a reactive oxygen species-associated mechanism

Mon, 11 May 2020 00:00:00 +0800

Cadmium (Cd) is one of the most widespread and toxic heavy metal to plants, and extracellular ATP (exATP) is thought to be an extracellular effector in regulating the physiological responses of plant cells to environmental stresses. However, the functions of exATP in the Cd-stressed plant cells is much unknown. The present work showed that treatment of tobacco (Nicotiana tabacum L. cv. Bright Yellow-2) cell-suspension cultures with exogenous CdCl₂ reduced the cell viability, exATP level and Mg content. However, the production of reactive oxygen species (ROS), Cd content, and electrolyte leakage of the cells were enhanced by exogenous CdCl₂. When the Cd-induced accumulation of ROS was decreased by the supplement with DMTU (dimethylthiourea, a scavenger of ROS), the Cd-induced increases of electrolyte leakage and Cd content were alleviated, and the Cd-induced reductions of cell viability were partly rescued, suggesting that Cd-induced reduction of cell viability is related to the ROS accumulation. Under the condition of Cd stress, when the reduction of exATP level was partly rescued by exogenous ATP (20 µM), the increases of ROS production, electrolyte leakage, and Cd content were attenuated, and the reduction of cell viability were also alleviated. These observations indicate that exATP can regulate the cell viability in the Cd–stressed plant cells possibly by a ROS-associated mechanism.

The MicroRNA-145-3p suppresses T-cell acute lymphoblastic leukemia cell malignant behaviors via the inhibition of NF-kappaB signaling pathway

Xin YANG — Mon, 11 May 2020 00:00:00 +0800

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells. Emerging studies have stated that microRNAs (miRNAs) may play key roles in the progression of T-ALL. This study aimed to investigate the role of miR-145-3p in T-ALL cell proliferation, invasion and apoptosis with the involvement of the nuclear factor-kappaB (NF-κB) signaling pathway. T-ALL Jurkat cells were harvested and the expression of miR-145-3p and NF-κB-p65 was measured. Gain- and loss- of function of miR-145-3p and NF-κB-p65 was performed to identify their roles in the biological behaviors in Jurkat cells including proliferation, cell cycle, apoptosis and invasion. The current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells. miR-145-3p directly bound to the 3’ untranslated region of NF-κB-p65 and suppressed its expression. Over-expression of miR-145-3p inhibited Jurkat cell proliferation, invasion and resistance to apoptosis, while over-expression of NF-κB-p65 presented an opposite trend. Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone, while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone. Taken together, this study provided evidence that miR-145-3p could suppress proliferation, invasion and resistance to death of T-ALL cells via inactivating the NF-κB signaling pathway.

Harmful Effect of Pyrethroid Esters Insecticide on Male Reproductive System Mainly Through Affecting Testicular Function and Inflammatory Markers.

Mohamed G. Elharrif — Mon, 11 May 2020 00:00:00 +0800

Pyrethroid esters are widely used as insecticides among worldwide. We aimed in this study to evaluate the harmful effect of deltamethrin on male reproductive system through assessment of reproductive hormones, inflammatory markers and testicular function. To achieve our aim, eighty male albino rats, 7-9 weeks were taken, weighed and divided into four experimental groups. First group kept as control group and other three groups given deltamethrin orally by different concentration 0.87, 8.7 and 17.4 mg/kg B.W repetitively for nine weeks duration. The results indicated that deltamethrin administration associated with a significant decrease in reproductive hormones especially FSH, LH and significance elevation in interluken2(IL2), interluken6(IL6), histamine and cortisol levels. Also significance inhibition of sperm motility and viability, decreased testis weights, sperm count and fructose in semen were noted. These finding clarify the harmful effect of deltamethrin on male reproductive system by producing significant alteration in reproductive hormones, inflammatory markers as well as testicular function.

Dephosphorylated mutations affect the protein-protein interactions of ERF in Populus simonii x P. nigra

Yao Sun, Yao Li, Xin Sun, Qiong Wu, Lei Wang — Mon, 11 May 2020 00:00:00 +0800

Phosphorylation is one common type of post-translational modification. It plays a vital role in many cellular processes. The reversible phosphorylation and dephosphorylation will affect protein structures and protein-protein interactions. Previously, we obtained 5 proteins from the cDNA library of Populus simonii x P. nigra that can interact with ethylene responsive factor (ERF). To study the effect of dephosphorylation of PsnERF on its protein binding ability, we predicted the putative phosphorylation sites and serine-rich region. The protein-binding affinity of different phosphorylation forms of PsnERF was demonstrated by yeast two hybrid assay (Y2H). The secondary structure and 3D structure of PsnERF, ERFm, TrunERF and PsnERF^197/198/202a was predicted by homology modeling.The Y2H assay indicated that deletion of serine-rich regions will not affect the interactions, while interactions are blocked for dephosphorylated ERF. Homology modeling results suggested that the protein-binding activity was affected by dephosphorylation and the S197/S198/S202 residues of PsnERF may be the key phosphorylation sites that influence its binding ability.