Abstract: : The human respiratory system consists of the upper and the lower respiratory tracts. Anatomically, the lower respiratory tract consists of 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. Previous studies mainly focused on AT2 cells; this review summarizes the current studies on lung development and property of AT1 cells.

Abstract: Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and can protect against multiple organs, also used as functional food to adjust the balance of the human body, but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim of the present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows: normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, then exposed to a single scrotal heat treatment (43 degrees C, 18min) on the 7th day. After HS treatment, the morphology of testis and epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells in destructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. After administration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels and superoxide dismutase (SOD) activity, glutathione (GSH) content significantly (p < 0.01) increase compared with the HS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) (p < 0.05 or p < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and heat shock protein 70 (HSP70) but also modulating the Bcl-2 family (p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase (MAPK) signaling pathways (p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibited potent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.

Abstract: The ancestral cultures have described many therapeutic properties of garlic; therefore, it is of central interest to elucidate the molecular basis explaining this millenary empirical knowledge. Indeed, it has been demonstrated a neuroprotective effect of allicin-a phytochemical present in garlic- linked to oxidative-inflammatory modulation. Allicin improved neuronal injury by heat shock protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) regulation. Also, allicin exerts renal protection involving a possible angiotensin type 1 receptor (AT1) interaction. In connection, AT1 overexpression has been recognized as a central deleterious factor in many brain diseases. However, there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to neuroinflammation. Thus, our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance axis. For this study, a murine microglial cell line (BV-2) was injured with lipopolysaccharides and treated or not with allicin. Then, it was evaluated cell viability, proinflammatory cytokine levels, cellular oxidative stress, iNOS, Hsp70, and AT1 protein expression (cellular and mitochondrial fractions), nitrite levels, and protein-protein interactions. The results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-iNOS counterbalance axis linked to direct protein-protein interaction.

Abstract: An FDA approved drug Cisplatin (CIS) (Cic-diamminedichloroplatinum [II]; CDDP; Platinol) is an anti-neoplastic which serves as a potential treatment option for the treatment of a variety of cancers and led to improve cure and survival rate. Alantolactone (ALT) is a sesquiterpene compound derived from Innula helinum and possesses potent anticancer activities against different cancers. The present study was conducted whether the ALT enhance the CIS anticancer activity or not? First we explored the different concentrations of ALT and CIS and found that the ALT at 20 µM could enhance the activity of CIS (80 µM). ALT at 20 µM induced apoptosis and inhibit the growth of A549 cells while CIS (80 µM) failed to inhibit or induced apoptosis in A549 cells while in combination they dramatically increased apoptosis in A549 cells. ALT and CIS in combination inhibit the STAT-3 at tyrosine 705, surviving, Bcl-2, Bclxl and increased the expression of Bax, cleaved (Cl)-caspase-3 and cl-parp and led the A549 cell to apoptosis. Our findings suggest that the ALT and CIS might be a good therapeutic approach to improve the efficacy of CIC in lung adenocarcinoma.

Abstract: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide, particularly in developing countries. A rapid and efficient method for TB diagnosis is indispensable to check the trend of tuberculosis expansion. The emergence of drug-resistant bacteria has increased the challenge of rapid drug resistance tests. Due to its high specificity and sensitivity, bacteriophage-based diagnosis is intensively pursued. In this review, we mainly described mycobacteriophage-based diagnosis in TB detection, especially two prevalent approaches: fluorescent reporter phage and phage amplified biologically assay (PhaB). The rationale of reporter phage is that phage carrying fluorescent genes can infect host bacteria specifically. Phage amplified biological assay based on the principle that phages can infect the live Mycobacterium tuberculosis in the specimen under suitable conditions and produce plaques. Other phage-based diagnostic methods, such as a combination of the amplified biologically assay and nucleic acid amplification or lateral flow assays, are also actively explored. This review will help us improve the understanding of mycobacteriophages in TB detection and better promote the development of the rapid diagnosis of M. tuberculosis.

Abstract: It is known that the high electronegativity of fluorine affects various soft tissues, especially the bone structure in organisms. Of these tissues are the kidneys, which play an important role in the excretion of fluoride from the body. Fluoride affects many cellular mechanisms. One of these effects is DNA damage. Our study aimed to investigate the likely protective effect of cholecalciferol (vitamin D3) on genomic DNA damage-induced NaF depending on concentration and time. The IC25 and IC50 values of NaF for 3, 12 and 24 h and optimum dose of increase in proliferation to vitamin D3 through MTT assay in NRK-52E kidney cells were determined. DNA damage was significantly increased (p < 0.05) compared to the control group in all groups except for vitamin D3. It was determined that treatment with NaF together with vitamin D3 decreased the DNA damage compared to NaF treated groups for 3 and 12 h. NaF combined with vitamin D3 was determined statistically to decrease (p < 0.05) DNA damage compared to NaF treated groups for 24 h. As a result, it was determined that the treatment with cytotoxic concentration NaF depending on the time significantly increased (p < 0.05) the genomic DNA damage, but NaF treatment together with vitamin D3 decreased the DNA damage in renal cells depending on the time. It was concluded that vitamin D3 may be useful in preventing DNA damage caused by NaF.

Abstract: In this study, we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α (HIF1α) 1772C/T gene polymorphism (rs 11549465) and renal cell carcinoma (RCC)/prostate cancer risk. We searched for relevant studies (before March 1, 2019) on Cochrane Library, Embase, and PubMed. Studies meeting the inclusion criteria were recruited into this meta-analysis. The outcome of dichotomous data was showed in the way of odds ratios (OR), and 95% confidence intervals (CI) were also counted. In this investigation, there was no association between HIF1α 1772C/T gene polymorphism and susceptibility to RCC in Caucasians, Asians as well as overall populations. In addition, HIF1α 1772C/T gene polymorphism was not found to be relevant to the survival in RCC. Interestingly, the T allele was relevant to prostate cancer risk in all populations, but not in Caucasians and Asians. However, the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian, Caucasian, and all populations. In conclusion, the T allele of the HIF1α 1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

Abstract: ULK1 (unc-51 like autophagy activating kinase 1), a mammalian serine/threonine kinase, is a key component of autophagy initiation complex and helps to induce all types of autophagy. Canonical autophagy is a process in which, through the interactions of a series of autophagy-related proteins, damaged organelles or misfolded proteins are engulfed by autophagosomes and then merged with lysosomes to be degraded. Thus, canonical autophagy is an important constituent part of the cellular “quality control.” Besides, accumulating evidence indicates that ULK1 exerts autophagy-independent effects in a cell-specific manner. For example, ULK1 facilitates neurite elongation through the regulation of endoplasmic reticulum (ER)–Golgi trafficking in neurons, stimulates phosphopentose pathway to help NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) production, and acts as a duplex regulator in type I IFN (type I interferon) induced innate immune response. Considering the importance and diversity of ULK1 in various biological processes, this review aims to present a comprehensive overview of autophagy and non-autophagy related functions of ULK1 in a variety of human physiological, pathological, and disease processes.

Abstract: : Residual ridge resorption (RRR) is the decrease in the jaw structure that follows tooth extraction. It is a multifactorial disorder, but reports on the associated genetic factors are scarce, particularly amongst the Saudis. This study aimed to investigate the role of single nucleotide polymorphisms (SNPs) in fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2) in RRR development in Saudis. The study included 192 individuals (RRR = 96; controls = 96) attending outpatient clinics at the College of Dentistry, King Saud University. Demographic and clinical data were collected, the digital panoramic dental radiograph was obtained, and mandibular residual ridge height was measured. DNA was extracted from saliva and genotyping was conducted on “Sequenom MassARRAY iPLEX”. Genotype and allele frequencies of three SNPs were calculated and compared. The age at first diagnosis and bone height were compared in the three genotypes of each SNP. The age of the patients, age at first edentulism, and bone height ranged 21-80 years, 12-70 years, and 13-34.6 mm, respectively. All three genotypes of the studied SNPs (rs2279351, rs78054962 and rs2306852) were identified. SNP rs2279351 associated significantly with RRR, and the mutant C allele was highly predisposing. No association was observed for the other two SNPs. The genotypes of all SNPs had an influence on age at first edentulism and bone height, but the results were not statistically different. Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity, it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone. SNP rs2279351 may alter its expression and hence RRR development. This study is limited due to small a sample size, and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.

Abstract: Elemental sulfur has been used as a traditional Chinese medicine to treat the late-onset hypogonadism and impotence without a clarified mechanism for many hundreds of years. In the present study, mice were received sulfur or distilled water for 35 days by daily intragastric gavage at a dose of 250 mg/kg body weight. Then, the serum testosterone level and genes associated with testicular testosterone biosynthesis (TTB) were detected. The gut microbiota was also analyzed by 16S rRNA gene sequencing. Serum testosterone level was significantly increased by 291.1% in sulfur-treated mice. The H2S levels in serum and feces were significantly increased. The expression of genes associated with TTB including StAR, p450c17, 3β-HSD, and P450scc in testes were significantly upregulated by Sulfur and NaHS, suggesting that sulfur promotes TTB depending on H2S. In addition, sulfur increased the diversity of gut microbiota and the abundance of several bacteria associated with sulfur metabolism, including genus Prevotella, which might be positively associated with serum level of testosterone in boys. Five pathways including bile secretion, carotenoid biosynthesis, lipid biosynthesis proteins, propanoate metabolism, and biosynthesis of type II polyketide products, were identified to associate with sulfur. Together, our results suggested that sulfur upregulated testicular testosterone biosynthesis via H2S, which was associated with alteration of gut microbiota in mice. Our study highlights a mechanism for the treatment of late-onset hypogonadism and impotence by sulfur.