Microbial metabolites are involved in tumorigenesis and development by regulating immune responses

The human microbiota is symbiotic with the host and can create a variety of metabolites. Under normal conditions, microbial metabolites can regulate host immune function and eliminate abnormal cells in a timely manner. However, when metabolite production is abnormal, the host immune system might be unable to identify and get rid of tumor cells at the early stage of carcinogenesis, which results in tumor development. The mechanisms by which intestinal microbial metabolites, including short-chain fatty acids (SCFAs), microbial tryptophan catabolites (MTCs), polyamines (PAs), hydrogen sulfide, and secondary bile acids, are involved in tumorigenesis and development by regulating immune responses are summarized in this review. SCFAs and MTCs can prevent cancer by altering the expression of enzymes and epigenetic modifications in both immune cells and intestinal epithelial cells. MTCs can also stimulate immune cell receptors to inhibit the growth and metastasis of the host cancer. SCFAs, MTCs, bacterial hydrogen sulfide and secondary bile acids can control mucosal immunity to influence the occurrence and growth of tumors. Additionally, SCFAs, MTCs, PAs and bacterial hydrogen sulfide can also affect the anti-tumor immune response in tumor therapy by regulating the function of immune cells. Microbial metabolites have a good application prospect in the clinical diagnosis and treatment of tumors, and our review provides a good basis for related research

Comparative genomics reveals cellobiose hydrolysis mechanism of Ruminiclostridium thermocellum M3, a cellulosic saccharification bacterium

The cellulosome of Ruminiclostridium thermocellum was one of the most efficient cellulase systems in nature. However, the product of cellulose degradation by R. thermocellum is cellobiose, which leads to the feedback inhibition of cellulosome, and it limits the R. thermocellum application in the field of cellulosic biomass consolidated bioprocessing (CBP) industry. In a previous study, R. thermocellum M3, which can hydrolyze cellulosic feedstocks into monosaccharides, was isolated from horse manure. In this study, the complete genome of R. thermocellum M3 was sequenced and assembled. The genome of R. thermocellum M3 was compared with the other R. thermocellum to reveal the mechanism of cellulosic saccharification by R. thermocellum M3. In addition, we predicted the key genes for the elimination of feedback inhibition of cellobiose in R. thermocellum. The results indicated that the whole genome sequence of R. thermocellum M3 consisted of 3.6 Mb of chromosomes with a 38.9% of GC%. To be specific, eight gene islands and 271 carbohydrate-active enzyme-encoded proteins were detected. Moreover, the results of gene function annotation showed that 2,071, 2,120, and 1,246 genes were annotated into the Clusters of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, and most of the genes were involved in carbohydrate metabolism and enzymatic catalysis. Different from other R. thermocellum, strain M3 has three proteins related to β-glucosidase, and the cellobiose hydrolysis was enhanced by the synergy of gene BglA and BglX. Meanwhile, the GH42 family, CBM36 family, and AA8 family might participate in cellobiose degradation

Correction: Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells.

[This corrects the article DOI: 10.18632/oncotarget.21306.]

Effect of Different Dilution Methods and Ratios of Ram Semen on Sperm Parameters after Cryopreservation

The dilution method and ratio were tested to assess their effects on the Hu ram semen after cryopreservation. Experiment I aimed to explore the effect of various dilution ratios (1:1, 1:2, 1:3, 1:4) of diluent I (Tris-based and egg yolk) under the condition of 1:1 dilution of diluent II (diluent I and glycerol) on the Hu ram semen preserved in liquid nitrogen regarding spermatozoa motility and kinetic parameters. Experiment II aimed to investigate the effect of various dilution ratios (1:1, 1:2, 1:3, 1:4) of diluent I under the condition of 1:2 dilution of diluent II to the Hu ram semen for cryopreservation on spermatozoa motility and kinetic parameters. The purpose of experiment III is to assess the effect of various dilution methods and ratios on the cryopreservation of Hu ram semen by detecting spermatozoa motility, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level. Experiment III includes four groups: one-step dilution method and two-step dilution method. The two-step dilution method includes two groups: 1:2, 1:1 and 1:3, 1:2, and the one-step dilution method includes two groups: 1:5 and 1:11. The results indicated that the post-thawed spermatozoa total motility (TM), progressive motility (PM) and average motion degree (MAD) were highest in the 1:2 group and significantly higher (p p p p Hu ram semen after cryopreservation

Effects of Different Diluents and Freezing Methods on Cryopreservation of Hu Ram Semen

The purpose of this study was to investigate the effects of different diluents and freezing methods on the quality of thawed sperm after cryopreservation and find an inexpensive and practical method for freezing Hu ram semen for use in inseminations under farm conditions. Ejaculates were collected from five Hu rams. In experiment I, ejaculates were diluted with eight different freezing diluents (basic diluents A, B, C, D, E, F, G, and H). After dilution and cooling, the samples were loaded into 0.25 mL straws and frozen using the liquid nitrogen fumigation method. In experiment II, diluent C was used as the basic diluent and the semen was frozen using liquid nitrogen fumigation and two program-controlled cooling methods. For analysis, frozen samples were evaluated in terms of motility parameters (total motility (TM), progressive motility (PM)), biokinetic characteristics (straight-line velocity (VSL), average path velocity (VAP), curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD)), reactive oxygen species (ROS) level, and membrane and acrosome integrity. In experiment I, diluent C had higher TM, PM, and acrosome and membrane integrity and lower ROS compared to other extenders (p p p > 0.05) amongst the three freezing methods. Liquid nitrogen fumigation resulted in higher (p < 0.05) PM, membrane integrity, acrosome integrity, and lower ROS level compared to the program. In conclusion, the thawed semen diluted with diluent C had higher quality compared to other diluents. The liquid nitrogen fumigation demonstrated superior semen cryopreservation effects compared to the program-controlled cooling method using diluent C

Effect of fumigation height and time on cryopreservation of ram semen

Abstract The cooling rate is a crucial factor in the process of freezing semen, influencing the overall freezing effectiveness. The height and time of fumigation can significantly impact the rate of cooling. Appropriate cooling rates can help minimize the formation of ice crystals in spermatozoa and reduce potential damage to them. Therefore, the aim of this study was to evaluate the effect of different fumigation heights and time for the cryopreservation of Hu ram semen. Experiments I–IV assessed the effect of semen cryopreservation by testing the post-thawed spermatozoa total motility (TM), progressive motility (PM) and kinetic parameters fumigated at distances of 2, 4, 6 and 8 cm for durations of 5, 10, 15 and 20 min, respectively. Based on the results of experiments I to IV, experiment V evaluated the effect of semen cryopreservation by testing the post-thawed spermatozoa TM, PM, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level fumigated at distances of 2, 4, 6 and 8 cm for duration of 20 min. The results indicated that fumigation at 2 cm for 20 min significantly (P < 0.05) improved spermatozoa TM, PM, mean angular displacement (MAD), plasma membrane integrity and acrosome integrity compared to other groups. Additionally, it significantly (P < 0.05) reduced spermatozoa ROS level compared to the 6 and 8 cm groups. In conclusion, fumigation for 20 min at a distance of 2 cm from the liquid nitrogen surface is the most suitable cooling method for the cryopreservation of Hu ram semen

Hormesis Research in China Is More Prevalent than Previously Thought

An analysis of China’s domestic publications revealed that China’s hormesis-related research was enormously underestimated. China’s documented hormesis-related research spans at least four decades, covers a broad spectrum of research areas, and is more abundant than previously thought. These findings should be considered in historical assessments of the concept of hormesis. Moreover, similar to the international literature, different terms have been used to describe the same phenomenon (hormesis), which hampers communication, generalization of findings and accumulation of knowledge. Hence, we advocate that ‘hormesis’ should be cited as a keyword in all the relevant publications written in Chinese language

Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells.

Migration of cancer cells leads to the invasion of distant organs by primary tumors. Further, endogenous electric fields (EFs) in the tumor microenvironment direct the migration of lung cancer cells by a process referred to as electrotaxis - although the precise mechanism remains unclear. Caveolin-1 (Cav-1) is a multifunctional scaffolding protein that is associated with directional cell migration and lung cancer invasion; however, its precise role in lung cancer electrotaxis is unknown. In the present study, we first detected outward electric currents on the tumor body surface in lung cancer xenografts using a highly-sensitive vibrating probe. Next, we found that highly-metastatic H1650-M3 cells migrated directionally to the cathode. In addition, reversal of the EF polarity reversed the direction of migration. Mechanistically, EFs activated Cav-1 and the downstream signaling molecule STAT3. RNA interference of Cav-1 reduced directional cell migration, which was accompanied by dampened STAT3 activation. Furthermore, pharmacological inhibition of STAT3 significantly reduced the electrotactic response, while rescue of STAT3 activation in Cav-1 knock-down cells restored electrotaxis. Taken together, these results suggest that endogenous EFs in the tumor micro-environment might play an important role in lung cancer metastasis by guiding cell migration through a Cav-1/STAT3-mediated signaling pathway

Correction: Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer cells.

[This corrects the article DOI: 10.18632/oncotarget.21306.]