Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma.

In light of a global rise in the number of patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of hepatocellular carcinoma (HCC), with the annual occurrence of MASLD-driven HCC expected to increase by 45%-130% by 2030. Although MASLD has become a serious major public health threat globally, the exact molecular mechanisms mediating MASLD-driven HCC remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on the utility of bioactive compounds to halt the progression of MASLD to MASLD-driven HCC. In this review, we first briefly review the recent progress of the possible mechanisms of pathogenesis and progression for MASLD-driven HCC. We then discuss the application of bioactive compounds to mitigate MASLD-driven HCC through different modulatory mechanisms encompassing anti-inflammatory, lipid metabolic, and gut microbial pathways, providing valuable information for future treatment and prevention of MASLD-driven HCC. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of MASLD-driven HCC is still warranted.

Transcriptome Analyses of Barley Roots Inoculated with Novel Paenibacillus sp. and Erwinia gerundensis Strains Reveal Beneficial Early-Stage Plant-Bacteria Interactions.

Plant growth-promoting bacteria can improve host plant traits including nutrient uptake and metabolism and tolerance to biotic and abiotic stresses. Understanding the molecular basis of plant-bacteria interactions using dual RNA-seq analyses provides key knowledge of both host and bacteria simultaneously, leading to future enhancements of beneficial interactions. In this study, dual RNA-seq analyses were performed to provide insights into the early-stage interactions between barley seedlings and three novel bacterial strains (two Paenibacillus sp. strains and one Erwinia gerundensis strain) isolated from the perennial ryegrass seed microbiome. Differentially expressed bacterial and barley genes/transcripts involved in plant-bacteria interactions were identified, with varying species- and strain-specific responses. Overall, transcriptome profiles suggested that all three strains improved stress response, signal transduction, and nutrient uptake and metabolism of barley seedlings. Results also suggested potential improvements in seedling root growth via repressing ethylene biosynthesis in roots. Bacterial secondary metabolite gene clusters producing compounds that are potentially associated with interactions with the barley endophytic microbiome and associated with stress tolerance of plants under nutrient limiting conditions were also identified. The results of this study provided the molecular basis of plant growth-promoting activities of three novel bacterial strains in barley, laid a solid foundation for the future development of these three bacterial strains as biofertilisers, and identified key differences between bacterial strains of the same species in their responses to plants.

Transcriptomics differentiate two novel bioactive strains of Paenibacillus sp. isolated from the perennial ryegrass seed microbiome.

Paenibacillus species are Gram-positive bacteria that have been isolated from a diverse array of plant species and soils, with some species exhibiting plant growth-promoting (PGP) activities. Here we report two strains (S02 and S25) of a novel Paenibacillus sp. that were isolated from perennial ryegrass (Lolium perenne) seeds. Comparative genomics analyses showed this novel species was closely related to P. polymyxa. Genomic analyses revealed that strains S02 and S25 possess PGP genes associated with biological nitrogen fixation, phosphate solubilisation and assimilation, as well as auxin production and transportation. Moreover, secondary metabolite gene cluster analyses identified 13 clusters that are shared by both strains and three clusters unique to S25. In vitro assays demonstrated strong bioprotection activity against phytopathogens (Colletotrichum graminicola and Fusarium verticillioides), particularly for strain S02. A transcriptomics analysis evaluating nitrogen fixation activity showed both strains carry an expressed nif operon, but strain S02 was more active than strain S25 in nitrogen-free media. Another transcriptomics analysis evaluating the interaction of strains with F. verticillioides showed strain S02 had increased expression of core genes of secondary metabolite clusters (fusaricidin, paenilan, tridecaptin and polymyxin) when F. verticillioides was present and absent, compared to S25. Such bioactivities make strain S02 a promising candidate to be developed as a combined biofertiliser/bioprotectant.

Profiling, isolation and characterisation of beneficial microbes from the seed microbiomes of drought tolerant wheat.

Climate change is predicted to increase the incidence and severity of drought conditions, posing a significant challenge for agriculture globally. Plant microbiomes have been demonstrated to aid crop species in the mitigation of drought stress. The study investigated the differences between the seed microbiomes of drought tolerant and drought susceptible wheat lines. Furthermore, it highlighted and quantified the degree of drought tolerance conferred by specific microbes isolated from drought tolerant wheat seed microbiomes. Metagenomic and culture-based methods were used to profile and characterise the seed microbiome composition of drought tolerant and drought susceptible wheat lines under rainfed and drought conditions. Isolates from certain genera were enriched by drought tolerant wheat lines when placed under drought stress. Wheat inoculated with isolates from these targeted genera, such as Curtobacterium flaccumfaciens (Cf D3-25) and Arthrobacter sp. (Ar sp. D4-14) demonstrated the ability to promote growth under drought conditions. This study indicates seed microbiomes from genetically distinct wheat lines enrich for beneficial bacteria in ways that are both line-specific and responsive to environmental stress. As such, seed from stress-phenotyped lines represent an invaluable resource for the identification of beneficial microbes with plant growth promoting activity that could improve commercial crop production.

Novel Xanthomonas Species From the Perennial Ryegrass Seed Microbiome - Assessing the Bioprotection Activity of Non-pathogenic Relatives of Pathogens.

The productivity of the Australian dairy industry is underpinned by pasture grasses, and importantly perennial ryegrass. The performance of these pasture grasses is supported by the fungal endophyte Epichloë spp. that has bioprotection activities, however, the broader microbiome is not well characterized. In this study, we characterized a novel bioprotectant Xanthomonas species isolated from perennial ryegrass (Lolium perenne L. cv. Alto). In vitro and in planta bioassays against key fungal pathogens of grasses (Sclerotium rolfsii, Drechslera brizae and Microdochium nivale) indicated strong bioprotection activities. A complete circular chromosome of ∼5.2 Mb was generated for three strains of the novel Xanthomonas sp. Based on the 16S ribosomal RNA gene, the strains were closely related to the plant pathogen Xanthomonas translucens, however, comparative genomics of 22 closely related xanthomonad strains indicated that these strains were a novel species. The comparative genomics analysis also identified two unique gene clusters associated with the production of bioprotectant secondary metabolites including one associated with a novel nonribosomal peptide synthetase and another with a siderophore. The analysis also identified genes associated with an endophytic lifestyle (e.g., Type VI secretion system), while no genes associated with pathogenicity were identified (e.g., Type III secretion system and effectors). Overall, these results indicate that these strains represent a novel, bioactive, non-pathogenic species of the genus Xanthomonas. Strain GW was the designated type strain of this novel Xanthomonas sp.

Design and evaluation of a biosynthesized cellulose drug releasing duraplasty.

Decompressive craniectomy (DC) is a standard surgical procedure performed on stroke patients in which a portion of a skull is removed and a duraplasty membrane is applied onto the brain. While DC can significantly reduce the risk of death, it does not reverse the stroke damage. In this study, a novel biosynthesized cellulose (BC)-based drug releasing duraplasty was developed and studied. The BC duraplasty fabrication process allowed readily incorporation of growth factors (GFs) in a sterile manner and control of physical and mechanical properties of the resulting duraplasty. Our results showed that BC duraplasty containing the highest amount of dry cellulose presented swelling ratio of 496 ± 27%, Young's modulus of 0.37 ± 0.02 MPa, ultimate tensile strength of 0.96 ± 0.02 MPa, while releasing GFs for over 10 days. In addition, neural stem/progenitor cell (NSPC) cultures demonstrated that the GFs released from the BC duraplasty promoted NSPC proliferation and differentiation in vitro. Finally, animal studies revealed that the BC duraplasty did not cause any inflammatory reactions after the DC procedure in vivo. In summary, this newly developed GF loaded BC membrane demonstrates a promising potential as drug releasing duraplasty, not only for stroke treatments but also for traumatic brain injuries and spinal cord injuries.

Wen-Xin Decoction ameliorates vascular endothelium dysfunction via the PI3K/AKT/eNOS pathway in experimental atherosclerosis in rats.

BACKGROUND: Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. However, excessive NO can cause lipid peroxidation and direct endothelial cell damage. Therefore, investigation of the role of NO in artherosclerosis development is important. Wen-Xin Decoction (WXD) has been shown to relieve myocardial ischemia reperfusion injury and prevent leukocyte adhesion and invasion; in addition, it can accelerate angiogenesis and prevent platelet activation and aggregation. In this study, we focused on the NO pathway to further clarify the protective effects of WXD on the vascular endothelium in rat models of artherosclerosis. METHODS: Wistar rats were randomly divided into a normal group (n = 10) and a model group (n = 75). Rat models of atherosclerosis were generated by intraperitoneal vitamin D3 (3 months) injections and administration of a high-fat diet (3 months with vitamin D3 and 2 months alone). The model rats were randomly divided into five groups (n = 15 each): model (saline), atorvastatin (4.8 mg/kg/d atorvastatin), high-dose WXD (9 g/kg/d), medium-dose WXD (4.5 g/kg/d), and low-dose WXD (2.25 g/kg/d) groups. Each group received continuous drug or saline administration (suspended liquid gavage) for 30 days, following which all animals were sacrificed. The ultrastructure and histopathological changes of vascular endothelial cells and the expression of PI3K/AKT/eNOS and iNOS in the thoracic aorta tissue were analyzed. RESULTS: WXD increased NO levels, modulated the NO/ET-1 ratio, and promoted repair of the injured vascular endothelium in a dose-dependent manner. At a high dose, WXD regulated the NO/ET-1 ratio as effectively as atorvastatin; furthermore, it increased NO levels within the physiological range to prevent endothelial damage caused by excessive NO expression. Real-time polymerase chain reaction and Western blot analysis showed that WXD significantly upregulated the mRNA and protein expressions of PI3K, AKT, and eNOS mRNA and significantly increased AKT and eNOS phosphorylation. CONCLUSIONS: Our results suggest that WXD protects and maintains the integrity of the vascular endothelium by activating the PI3K/AKT/eNOS pathway, decreasing iNOS expression, and promoting the release of physiological NO levels.

The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.

Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.

Prevalence of obesity among secondary school students from 2009 to 2014 in China: a meta-analysis.

BACKGROUND: In recent years, obesity was a major public health problem in many countries. It was estimated that 8% of their children are obese. However, little is known about the overall prevalence of obesity among secondary students in China, the aim of this study was to evaluate the overall obesity prevalence of student from Chinese secondary school. METHODS: Publications from 2009 to 2014 on the obesity prevalence among secondary school students in China were retrieved from PubMed, online Chinese periodical full-text databases of VIP, CNKI and Wan fang. Meta Analyst was used analyze the total rates of obesity for Chinese secondary school. RESULTS: After evaluation of the quality of the articles, 32 papers were finally included in our study, and the total sample sizes on the obesity investigation were 218317 (107631 male and 110686 female), in which 27455(14865 male and 12590 female) were obesity. Meta-analyst findings showed that the pooled prevalence of obesity in secondary school students are 8.4 %( 95% CI: 6.2%- 11.3%) and 4.8 %( 95% CI: 3.2%-7.2%) for boy and girl respectively. CONCLUSION: Our results suggest that school and government related department should pay more attention to the obesity among secondary school students in China, and take some properly measures should to curve the trend growth of obesity.

Antecedentes: En los últimos años, la obesidad es un importante problema de salud pública en muchos países. Se calcula que el 8% de los niños son obesos.Sin embargo, poco se sabe acerca de la prevalencia de la obesidad entre los alumnos de secundaria en China, el objetivo de este estudio fue evaluar la prevalencia de la obesidad en general chino, estudiante de la escuela secundaria. Métodos: Publicaciones de 2009 a 2014 en la prevalencia de obesidad entre los estudiantes de la escuela secundaria en China fueron recuperados de PubMed, Online Chinese periódico de bases de datos de texto completo de VIP, CNKI y Wan Fang.Analista del meta fue utilizado analizar el total de las tasas de obesidad para chinos de la escuela secundaria. Resultados: Después de la evaluación de la calidad de los artículos, 33 papeles fueron finalmente incluidos en nuestro estudio, y el total de los tamaños de muestra sobre la obesidad investigación fueron 218317 (107631 macho y 110686 hembra), en la que 27455 (14863 macho y 12590 mujeres) fueron la obesidad.Los resultados mostraron que el analista del meta la prevalencia de la obesidad en estudiantes de secundaria son 8,4% (IC del 95%: 6,2% - 11,3%) y 4,8% (IC del 95%: 3,2% - 7,2%) para chico y chica, respectivamente. Conclusión: Nuestros resultados sugieren que la escuela y Gobierno related Departamento debería prestar más atención a la obesidad entre los estudiantes de la escuela secundaria en China, y tomar algunas medidas adecuadamente a la curva de la tendencia de crecimiento de la obesidad.