Role of long non-coding RNAs and TGF-ß signaling in the regulation of breast cancer pathogenesis and therapeutic targets.

The cytokine known as transforming growth factor (TGF) is essential for cell development, differentiation, and apoptosis in BC. TGF-ß dysregulation can either promote or inhibit tumor development, and it is a key signaling pathway in BC spread. A recently identified family of ncRNAs known as lncRNAs has received a great deal of effort and is an important regulator of many cellular processes, including transcription of genes, chromatin remodeling, progression of the cell cycle, and posttranscriptional processing. Furthermore, both TGF-ß signaling and lncRNAs serve as important early-stage biomarkers for BC diagnosis and prognosis and also play a significant role in BC drug resistance. According to recent studies, lncRNAs can regulate TGF-ß by modulating its cofactors in BC. However, the particular functions of lncRNAs and the TGF-ß pathway in controlling BC progression are not well understood yet. This review explores the lncRNAs' functional properties in BC as tumor suppressors or oncogenes in the regulation of genes, with a focus on dysregulated TGF-ß signaling. Further, we emphasize the functional roles of lncRNAs and TGF-ß pathway in the progression of BC to discover new treatment strategies and better comprehend the fundamental cellular pathways.

Molecular Mapping to Discover Reliable Salinity-Resilient QTLs from the Novel Landrace Akundi in Two Bi-Parental Populations Using SNP-Based Genome-Wide Analysis in Rice.

Achieving high-yield potential is always the ultimate objective of any breeding program. However, various abiotic stresses such as salinity, drought, cold, flood, and heat hampered rice productivity tremendously. Salinity is one of the most important abiotic stresses that adversely affect rice grain yield. The present investigation was undertaken to dissect new genetic loci, which are responsible for salt tolerance at the early seedling stage in rice. A bi-parental mapping population (F2:3) was developed from the cross between BRRI dhan28/Akundi, where BRRI dhan28 (BR28) is a salt-sensitive irrigated (boro) rice mega variety and Akundi is a highly salinity-tolerant Bangladeshi origin indica rice landrace that is utilized as a donor parent. We report reliable and stable QTLs for salt tolerance from a common donor (Akundi) irrespective of two different genetic backgrounds (BRRI dhan49/Akundi and BRRI dhan28/Akundi). A robust 1k-Rice Custom Amplicon (1k-RiCA) SNP marker genotyping platform was used for genome-wide analysis of this bi-parental population. After eliminating markers with high segregation distortion, 886 polymorphic SNPs built a genetic linkage map covering 1526.5 cM of whole rice genome with an average SNP density of 1.72 cM for the 12 genetic linkage groups. A total of 12 QTLs for nine different salt tolerance-related traits were identified using QGene and inclusive composite interval mapping of additive and dominant QTL (ICIM-ADD) under salt stress on seven different chromosomes. All of these 12 new QTLs were found to be unique, as no other map from the previous study has reported these QTLs in the similar chromosomal location and found them different from extensively studied Saltol, SKC1, OsSalT, and salT locus. Twenty-eight significant digenic/epistatic interactions were identified between chromosomal regions linked to or unlinked to QTLs. Akundi acts like a new alternate donor source of salt tolerance except for other usually known donors such as Nona Bokra, Pokkali, Capsule, and Hasawi used in salt tolerance genetic analysis and breeding programs worldwide, including Bangladesh. Integration of the seven novel, reliable, stable, and background independent salinity-resilient QTLs (qSES1, qSL1, qRL1, qSUR1, qSL8, qK8, qK1) reported in this investigation will expedite the cultivar development that is highly tolerant to salt stress.

Exosomal circular RNAs: New player in breast cancer progression and therapeutic targets.

Breast cancer is the most prevalent type of malignancy among women. Exosomes are extracellular vesicles of cell membrane origin that are released via exocytosis. Their cargo contains lipids, proteins, DNA, and different forms of RNA, including circular RNAs. Circular RNAs are new class of non-coding RNAs with a closed-loop shape involved in several types of cancer, including breast cancer. Exosomes contained a lot of circRNAs which are called exosomal circRNAs. By interfering with several biological pathways, exosomal circRNAs can have either a proliferative or suppressive role in cancer. The involvement of exosomal circRNAs in breast cancer has been studied with consideration to tumor development and progression as well as its effects on therapeutic resistance. However, its exact mechanism is still unclear, and there have not been available clinical implications of exo-circRNAs in breast cancer. Here, we highlight the role of exosomal circRNAs in breast cancer progression and to highlight the most recent development and potential of circRNAas therapeutic targets and diagnostics for breast cancer.

Strategies to overcome the main challenges of the use of exosomes as drug carrier for cancer therapy.

Exosomes are naturally occurring nanosized particles that aid intercellular communication by transmitting biological information between cells. Exosomes have therapeutic efficacy that can transfer their contents between cells as natural carriers. In addition, the exosomal contents delivered to the recipient pathological cells significantly inhibit cancer progression. However, exosome-based tumor treatments are inadequately precise or successful, and various challenges should be adequately overcome. Here, we discuss the significant challenges that exosomes face as drug carriers used for therapeutic targets and strategies for overcoming these challenges in order to promote this new incoming drug carrier further and improve future clinical outcomes. We also present techniques for overcoming these challenges.

Biodiesel Exhaust Toxicity with and without Diethylene Glycol Dimethyl Ether Fuel Additive in Primary Airway Epithelial Cells Grown at the Air-Liquid Interface.

Biodiesel usage is increasing steadily worldwide as the push for renewable fuel sources increases. The increased oxygen content in biodiesel fuel is believed to cause decreased particulate matter (PM) and increased nitrous oxides within its exhaust. The addition of fuel additives to further increase the oxygen content may contribute to even further benefits in exhaust composition. The aim of this study was to assess the toxicity of 10% (v/v) diethylene glycol dimethyl ether (DGDME) added as a biodiesel fuel additive. Primary human airway epithelial cells were grown at the air-liquid interface and exposed to diluted exhaust from an engine running on either grapeseed, bran, or coconut biodiesel or the same three biodiesels with 10% (v/v) DGDME added to them; mineral diesel and air were used as controls. Exhaust properties, culture permeability, epithelial cell damage, and IL-6 and IL-8 release were measured postexposure. The fuel additive DGDME caused a decrease in PM and nitrous oxide concentrations. However, exhaust exposure with DGDME also caused decreased permeability, increased epithelial cell damage, and increased release of IL-6 and IL-8 (p < 0.05). Despite the fuel additive having beneficial effects on the exhaust properties of the biodiesel, it was found to be more toxic.

Genetic Mapping to Detect Stringent QTLs Using 1k-RiCA SNP Genotyping Platform from the New Landrace Associated with Salt Tolerance at the Seedling Stage in Rice.

Rice is the world's most important food crop, providing the daily calorie intake for more than half of the world's population. Rice breeding has always been preoccupied with maximizing yield potential. However, numerous abiotic factors, such as salt, cold, drought, and heat, significantly reduce rice productivity. Salinity, one of the major abiotic stresses, reduces rice yield worldwide. This study was conducted to determine new quantitative trait loci (QTLs) that regulate salt tolerance in rice seedlings. One F2:3 mapping population was derived from a cross between BRRI dhan49 (a popular but sensitive rainfed rice variety) and Akundi (a salt-tolerant rice landrace in Bangladesh used as a donor parent). The 1k-Rice Custom Amplicon (1k-RiCA) single-nucleotide polymorphism (SNP) markers were used to genotype this mapping population. After removing segregation distortion and monomorphic markers, 884 SNPs generated a 1526.8 cM-long genetic linkage map with a mean marker density of 1.7 cM for the 12 linkage groups. By exploiting QGene and ICIM-ADD, a sum of 15 QTLs for nine traits was identified in salt stress on seven chromosomes. Four important genomic loci were identified (qSES1, qSL1, qSUR1 and qRL1) on chromosome 1. Out of these 15 QTLs, 14 QTLs are unique, as no other study has mapped in the same chromosomal location. We also detected 15 putative candidate genes and their functions. The ICIM-EPI approach identified 43 significant pairwise epistasis interactions between regions associated with and unassociated with QTLs. Apart from more well-known donors, Akundi serves as an important new donor source for global salt tolerance breeding initiatives, including Bangladesh. The introgression of the novel QTLs identified in this study will accelerate the development of new salt-tolerant varieties that are highly resistant to salt stress using marker-enabled breeding.

Effects of Lifestyle Intervention on Inflammatory Markers and Waist Circumference in Overweight/Obese Adults With Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Physical inactivity and an imbalanced diet could lead to some cardio metabolic risk factors. OBJECTIVE: The objective of this meta-analysis was to investigate the effects of lifestyle modification on inflammatory indicators and waist circumference (WC) in overweight/obese subjects with metabolic syndrome (MS). DATA SOURCES: A systematic search was conducted in PubMed, CINAHL, MEDLINE, Cochrane, Google Scholar, and Web of Science. STUDY SELECTION: The selection criteria were randomized controlled trials (RCTs) investigating the effects of lifestyle interventions on inflammation and WC from inception to 20 December 2020. The weighted mean difference (WMD) and 95% confidence interval (CI) between interventions were computed using a random or fixed-effects model. RESULTS: Six RCTs (including 1246 MS patients who had, on average, overweight/obesity) met all inclusion criteria. Interventions lasted 6 to 12 months (2-5 sessions per week). Lifestyle intervention significantly reduced C-reactive protein (WMD: -0.52 mg/ml, 95% CI: -0.72, -0.33), IL-6 (WMD: -0.50 pg/ml, 95% CI: -0.56, -0.45), and increased adiponectin (WMD: 0.81 µg/ml, 95% CI, 0.64, 0.98). Moreover, lifestyle modification significantly decreased WC (WMD: -3.12 cm, 95% CI, -4.61, -1.62). CONCLUSION: Our findings provide evidence that lifestyle alterations, including physical activity and diet, can lead to significant improvement in abdominal obesity, measured by WC and some inflammation markers among overweight/obese individuals with MS. Further high-quality research is needed to clarify the mechanisms underlying the effect of such interventions on this population's inflammatory markers.

Exercise Training for Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Pulmonary hypertension (PH) is a chronic disease with a notable health burden; regular exercise may improve specific health outcome measures. OBJECTIVE: The objective of this meta-analysis was to estimate the effectiveness of exercise training for PH patients. DATA SOURCES: PubMed, CINAHL, SportDiscuss and Google Scholar databases and reference lists of included studies were searched. STUDY SELECTION: The selection criteria were randomized controlled trials (RCTs) employing an exercise training intervention. Data were extracted from the entered studies for analysis. The primary outcomes were peak oxygen uptake (VO2peak), anaerobic threshold (AT), 6-minute walk distance (6-MWD), and quality of life (QoL) measures (physical component score and mental component score). The analysis included 9 articles with a total of 302 participants: intervention (n = 154), and control (n = 148). RESULTS: In the pooled analysis, improvements were seen in: VO2peak, mean difference (MD) 2.79 ml/kg/min (95% CI 2.00 to 3.59, p < 0.00001); AT, MD 107.83 ml/min (95% CI 39.64 to 176.00, p = 0.002); and 6-MWD, MD 46.67 meters (95% CI 32.39 to 60.96, p < 0.00001). Differences were found in the SF-36 physical component score MD 3.57 (95% CI 2.04 to 5.10, p < 0.00001) and the SF-36 mental component score MD 3.92 (95% CI 1.92 to 5.91, p = 0.001). CONCLUSION: This meta-analysis demonstrates exercise training has a beneficial effect on fitness, walking performance, and self-reported QoL in PH patients.

Effect of small proportion of butanol additive on the performance, emission, and combustion of Australian native first- and second-generation biodiesel in a diesel engine.

This paper aims to investigate the effect of the addition of 5% alcohol (butanol) with biodiesel-diesel blends on the performance, emissions, and combustion of a naturally aspirated four stroke multi-cylinder diesel engine at different engine speeds (1200 to 2400 rpm) under full load conditions. Three types of local Australian biodiesel, namely macadamia biodiesel (MB), rice bran biodiesel (RB), and waste cooking oil biodiesel (WCB), were used for this study, and the data was compared with results for conventional diesel fuel (B0). Performance results showed that the addition of butanol with diesel-biodiesel blends slightly lowers the engine efficiency. The emission study revealed that the addition of butanol additive with diesel-biodiesel blends lowers the exhaust gas temperature (EGT), carbon monoxide (CO), nitrogen oxide (NOx), and particulate matter (PM) emissions whereas it increases hydrocarbon (HC) emissions compared to B0. The combustion results indicated that in-cylinder pressure (CP) for additive added fuel is higher (0.45-1.49%), while heat release rate (HRR) was lower (2.60-9.10%) than for B0. Also, additive added fuel lowers the ignition delay (ID) by 23-30% than for B0. Finally, it can be recommended that the addition of 5% butanol with Australian biodiesel-diesel blends can significantly lower the NOx and PM emissions.

Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis.

BACKGROUND: Liposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials. METHODS: We conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated. RESULTS: We identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2220 patients, of which1112 patients were treated with liposomal formulations and 1108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF(OR 0.34, 95% CI, 0.24-0.47), alopecia (OR 0.0.25, 95% CI, 0.0.10-0.62), neutropenia (OR 0.62, 95% CI, 0.45- 0.85),(OR 0.89, 95% CI, 0.71-1.125), and thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25). The incidence of PPE was similar in both arms (OR 1.08, 95% CI, 0.11- 10.30). CONCLUSIONS: Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea and vomiting compared with the conventional anthracyclines. The better therapeutic index of liposomal anthracyclines without compromising the efficacy makes it a favorable choice over conventional anthracyclines in elderly patients, patients with risk factors for cardiac disease and patients with prior use of anthracyclines.

Thin-film fixed-bed reactor for solar photocatalytic inactivation of Aeromonas hydrophila: influence of water quality.

BACKGROUND: Controlling fish disease is one of the major concerns in contemporary aquaculture. The use of antibiotics or chemical disinfection cannot provide a healthy aquaculture system without residual effects. Water quality is also important in determining the success or failure of fish production. Several solar photocatalytic reactors have been used to treat drinking water or waste water without leaving chemical residues. This study has investigated the impact of several key aspects of water quality on the inactivation of the pathogenic bacterium Aeromonas hydrophila using a pilot-scale thin-film fixed-bed reactor (TFFBR) system. RESULTS: The level of inactivation of Aeromonas hydrophila ATCC 35654 was determined using a TFFBR with a photocatalytic area of 0.47 m(2) under the influence of various water quality variables (pH, conductivity, turbidity and colour) under high solar irradiance conditions (980-1100 W m(-2)), at a flow rate of 4.8 L h(-1) through the reactor. Bacterial enumeration were obtained through conventional plate count using trypticase soy agar media, cultured in conventional aerobic conditions to detect healthy cells and under ROS-neutralised conditions to detect both healthy and sub-lethally injured (oxygen-sensitive) cells. The results showed that turbidity has a major influence on solar photocatalytic inactivation of A. hydrophila. Humic acids appear to decrease TiO(2) effectiveness under full sunlight and reduce microbial inactivation. pH in the range 7-9 and salinity both have no major effect on the extent of photoinactivation or sub-lethal injury. CONCLUSIONS: This study demonstrates the effectiveness of the TFFBR in the inactivation of Aeromonas hydrophila under the influence of several water quality variables at high solar irradiance, providing an opportunity for the application of solar photocatalysis in aquaculture systems, as long as turbidity remains low.

Thin-film fixed-bed reactor (TFFBR) for solar photocatalytic inactivation of aquaculture pathogen Aeromonas hydrophila.

BACKGROUND: Outbreaks of infectious diseases by microbial pathogens can cause substantial losses of stock in aquaculture systems. There are several ways to eliminate these pathogens including the use of antibiotics, biocides and conventional disinfectants, but these leave undesirable chemical residues. Conversely, using sunlight for disinfection has the advantage of leaving no chemical residue and is particularly suited to countries with sunny climates. Titanium dioxide (TiO2) is a photocatalyst that increases the effectiveness of solar disinfection. In recent years, several different types of solar photocatalytic reactors coated with TiO2 have been developed for waste water and drinking water treatment. In this study a thin-film fixed-bed reactor (TFFBR), designed as a sloping flat plate reactor coated with P25 DEGUSSA TiO2, was used. RESULTS: The level of inactivation of the aquaculture pathogen Aeromonas hydrophila ATCC 35654 was determined after travelling across the TFFBR under various natural sunlight conditions (300-1200 W m(-2)), at 3 different flow rates (4.8, 8.4 and 16.8 L h(-1)). Bacterial numbers were determined by conventional plate counting using selective agar media, cultured (i) under conventional aerobic conditions to detect healthy cells and (ii) under conditions designed to neutralise reactive oxygen species (agar medium supplemented with the peroxide scavenger sodium pyruvate at 0.05% w/v, incubated under anaerobic conditions), to detect both healthy and sub-lethally injured (oxygen-sensitive) cells. The results clearly demonstrate that high sunlight intensities (≥ 600 W m(-2)) and low flow rates (4.8 L h(-1)) provided optimum conditions for inactivation of A. hydrophila ATCC 3564, with greater overall inactivation and fewer sub-lethally injured cells than at low sunlight intensities or high flow rates. Low sunlight intensities resulted in reduced overall inactivation and greater sub-lethal injury at all flow rates. CONCLUSIONS: This is the first demonstration of the effectiveness of the TFFBR in the inactivation of Aeromonas hydrophila at high sunlight intensities, providing proof-of-concept for the application of solar photocatalysis in aquaculture systems.