Both siRNA and miRNA can serve as powerful gene-silencing reagents but their specific delivery to cancer cells in vivo without collateral damage to healthy cells remains challenging. We report here ...the application of RNA nanotechnology for specific and efficient delivery of anti-miRNA seed-targeting sequence to block the growth of prostate cancer in mouse models. Utilizing the thermodynamically ultra-stable three-way junction of the pRNA of phi29 DNA packaging motor, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-prostate-specific membrane antigen (PSMA) RNA aptamer as a targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The 16 nm RNase-resistant and thermodynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little or no accumulation in healthy organs 8 hours postinjection, and subsequently repressed tumor growth at low doses with high efficiency.
Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living ...with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai.
A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China. Logistic regression analysis was performed to analyze risk factors for drug resistance among HIV-infected people with virological failure. The related collected factors included patient age, gender, marital status, infection route, baseline CD4 count, antiretroviral therapy regimens, time between HIV diagnosis and initiating antiretroviral therapy. Factors with p<0.1 in the univariate logistic regression test were analyzed by multivariate logistic regression test.
There were 575 subjects selected for this study and 369 participated in this research. For the antiretroviral therapy drugs, the rates of transmitted drug resistance and acquired drug resistance were significantly different. The non-nucleoside reverse transcriptase inhibitor (NNRTI) had the highest drug resistance rate (transmitted drug resistance, 10.9%; acquired drug resistance, 53.3%) and protease inhibitors (PIs) had the lowest drug resistance rate (transmitted drug resistance, 1.7%; acquired drug resistance, 2.7%). Logistic regression analysis found no factors that were related to drug resistance except marital status (married status for tenofovir: odds ratio = 6.345, 95% confidence interval = 1.553-25.921, P = 0.010) and the time span between HIV diagnosis and initiating antiretroviral therapy (≤6M for stavudine: odds ratio = 0.271, 95% confidence interval = 0.086-0.850, P = 0.025; ≤6M for didanosine: odds ratio = 0.284, 95% confidence interval = 0.096-0.842, P = 0.023; ≤6M for tenofovir: odds ratio = 0.079, 95% confidence interval = 0.018-0.350,P<0.001).
NNRTI had a higher DR rate compared with nucleoside reverse transcriptase inhibitor (NRTI) and PIs, consequently, LPV/r was a reasonable choice for patients with NNRTI drugs resistance in China. Only married status and a time span≤6 month between the HIV confirmed date and the time initiating antiretroviral therapy were risk factors for TDF drug resistance. Both baseline HIV-RNA load and resistance test is crucial for TDR diagnosis, and frequent monitoring of HIV-RNA load is crucial for ADR identification and intervention. Treatment adherence still plays a positive role on the outcome of ART.
Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and ...high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases.
In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy.
Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells.
and
studies have demonstrated that stem cells are promising cell sources for the liver regeneration.
Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.
Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)-a free-radical gas-plus its endogenous producer ...NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.
Vitamin D is an important hormone that regulates many physiological processes related to human health. Through its nuclear receptor, VDR, vitamin D controls gene expression through genetic and ...epigenetic mechanisms. Increasing data have demonstrated the anti-cancer activities of vitamin D in various cancers, including colon cancer. This review summarizes the recent progresses in our understanding of the molecular mechanisms of vitamin D and its interaction with the epigenetic machinery in colon cancer. Vitamin D changes the status of DNA methylation and histone modifications, resulting in the activation of tumor suppressors and inhibition of oncogenes. In addition, vitamin D activates the expression of tumor suppressing miRNAs, which contribute to the tumor suppressive activity. Further understanding of the epigenetic action of vitamin D will help the development of therapeutic strategies targeting the vitamin D signaling pathway without inducing the hypercalcemic side effects.
Highlights
An interlayer confined strategy to realize the substitution of nitrogen terminals between Ti
3
C
2
MXene layers is proposed.
The targeted Ti
3
C
2
-N
funct
anode exhibits fast-charging ...ability and great superiority in cycle life at − 25 °C.
Ti
3
C
2
-N
funct
not only possesses a lower Na-ion diffusion energy barrier and charge transfer activation energy, but also exhibits Na
+
-solvent co-intercalation behavior at low temperature.
Sodium-ion batteries stand a chance of enabling fast charging ability and long lifespan while operating at low temperature (low-T). However, sluggish kinetics and aggravated dendrites present two major challenges for anodes to achieve the goal at low-T. Herein, we propose an interlayer confined strategy for tailoring nitrogen terminals on Ti
3
C
2
MXene (Ti
3
C
2
-N
funct
) to address these issues. The introduction of nitrogen terminals endows Ti
3
C
2
-N
funct
with large interlayer space and charge redistribution, improved conductivity and sufficient adsorption sites for Na
+
, which improves the possibility of Ti
3
C
2
for accommodating more Na atoms, further enhancing the Na
+
storage capability of Ti
3
C
2
. As revealed, Ti
3
C
2
-N
funct
not only possesses a lower Na-ion diffusion energy barrier and charge transfer activation energy, but also exhibits Na
+
-solvent co-intercalation behavior to circumvent a high de-solvation energy barrier at low-T. Besides, the solid electrolyte interface dominated by inorganic compounds is more beneficial for the Na
+
transfer at the electrode/electrolyte interface. Compared with of the unmodified sample, Ti
3
C
2
-N
funct
exhibits a twofold capacity (201 mAh g
−1
), fast-charging ability (18 min at 80% capacity retention), and great superiority in cycle life (80.9%@5000 cycles) at − 25 °C. When coupling with Na
3
V
2
(PO
4
)
2
F
3
cathode, the Ti
3
C
2
-N
funct
//NVPF exhibits high energy density and cycle stability at − 25 °C.
The dietary effect on gut health has long been recognized through the empirical practice of soothing gastric discomfort with certain types of food, and recently the correlation between specific diets ...with lower incidences of several gastrointestinal diseases has been revealed. Ingredients from those considered beneficial foods have been isolated and studied, and some of them have already been put into the supplement market. In this review, we focus on latest studies of these food-derived ingredients for their proposed preventive and therapeutic roles in gastrointestinal disorders, with the attempt of drawing evidence-based suggestions on consuming these products.
Lysozymes are naturally occurring enzymes present in a variety of biological organisms, such as bacteria, fungi, and animal bodily secretions and tissues. It is also the main ingredient of many ...ethnomedicines. It is well known that lysozymes and lysozyme-like enzymes can be used as anti-bacterial agents by degrading bacterial cell wall peptidoglycan that leads to cell death, and can also inhibit fungi, yeasts, and viruses. In addition to its direct antimicrobial activity, lysozyme is also an important component of the innate immune system in most mammals. Increasing evidence has shown the immune-modulatory effects of lysozymes against infection and inflammation. More recently, studies have revealed the anti-cancer activities of lysozyme in multiple types of tumors, potentially through its immune-modulatory activities. In this review, we summarized the major functions and underlying mechanisms of lysozymes derived from animal and plant sources. We highlighted the therapeutic applications and recent advances of lysozymes in cancers, hypertension, and viral diseases, aiming toseeking alternative therapies for standard medical treatment bypassing side effects. We also evaluated the role of lysozyme as a promising cancer marker for prognosis to indicate the outcomes recurrence for patients.
Metastasis leads to poor prognosis in colorectal cancer patients, and there is a growing need for new therapeutic targets. TMEM16A (ANO1, DOG1 or TAOS2) has recently been identified as a ...calcium-activated chloride channel (CaCC) and is reported to be overexpressed in several malignancies; however, its expression and function in colorectal cancer (CRC) remains unclear. In this study, we found expression of TMEM16A mRNA and protein in high-metastatic-potential SW620, HCT116 and LS174T cells, but not in primary HCT8 and SW480 cells, using RT-PCR, western blotting and immunofluorescence labeling. Patch-clamp recordings detected CaCC currents regulated by intracellular Ca(2+) and voltage in SW620 cells. Knockdown of TMEM16A by short hairpin RNAs (shRNA) resulted in the suppression of growth, migration and invasion of SW620 cells as detected by MTT, wound-healing and transwell assays. Mechanistically, TMEM16A depletion was accompanied by the dysregulation of phospho-MEK, phospho-ERK1/2 and cyclin D1 expression. Flow cytometry analysis showed that SW620 cells were inhibited from the G1 to S phase of the cell cycle in the TMEM16A shRNA group compared with the control group. In conclusion, our results indicate that TMEM16A CaCC is involved in growth, migration and invasion of metastatic CRC cells and provide evidence for TMEM16A as a potential drug target for treating metastatic colorectal carcinoma.
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