Therapeutic resistance of pancreatic cancer: Roadmap to its reversal

Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease.     

Construction of a rAAV-SaCas9 system expressing eGFP and its application to improve muscle mass

Biotechnology Letters - An ideal rAAV gene editing system not only effectively edits genes at specific site, but also prevents the spread of the virus from occurring off-target or carcinogenic...     

The relationship between anthocyanin accumulation and photoprotection in young leaves of two dominant tree species in subtropical forests in different seasons

Photosynthesis Research - Increasing amounts of experimental evidence show that anthocyanins provide physiological protection to plants under stress. However, the difference in photoprotection...     

GDF11 prevents the formation of thoracic aortic dissection in mice: Promotion of contractile transition of aortic SMCs

Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de-differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β-aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno-associated virus type 2 (AAV-2)-mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)-2, 3, 9 in aortic SMCs. The canonical TGF-β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de-differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD.     

Morphological provision for the specialization of hares to coprophagy: The architectonics of the mucous surface of the intestine

The macrostructure of the surface of the mucous membrane of the gastrointestinal tract were studied in detail in two hare species (Lepus europaeus and L. timidus) using scanning electron and digital microscopes. The morphology of the gastrointestinal tract of hares, which is similar in the two species studied, was described in detail. The macrostructure of the inner surface of the ileocecal junction was investigated. The particularities of the architectonics of the mucous membrane of the intestine that are specific for hares were revealed. In the jejunum of both hare species, the mucous membrane is represented by villi with merged bases, which form circular plates. The mucosa of the colon forms large conical villi, the surface of which is scattered with secreting cells. The possible functional significance of the revealed morphological particularities is discussed.     

Ataxin1L Is a Regulator of HSC Function Highlighting the Utility of Cross-Tissue Comparisons for Gene Discovery

Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein–protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.     

Thyroid Hormones and Activities of Lysosomal Proteolytic Enzymes in Organs of the Arctic Fox Alopex lagopus

Age-related changes of content of thyroid hormones in the blood serum and of activities of lysosomal proteinases in organs were studied in the arctic fox Alopex lagopus L. in early postnatal ontogenesis. The existence has been shown of a negative correlation between the age changes in the serum thyroxin content and lysosomal proteinase activities in some organs of these animals. The results obtained indicate predominance of anabolic function of thyroid hormones in arctic fox cubs. The problem of anabolic and catabolic effects of thyroid hormones on protein metabolism is discussed.