Beneath the Surface: Exploring Hidden Threats of Long-Term Corticosteroid Therapy to Bone Density.

Within the field of medical treatments, corticosteroids are potent substances that efficiently reduce inflammation and immunological responses, making them essential for the management of a wide range of medical ailments. However, continued use of these synthetic drugs presents a serious risk: the onset of osteoporosis brought on by corticosteroids. Determining the complex pathways by which corticosteroids cause a general disturbance in bone metabolism, suppress osteoblast function, increase osteoclast activity, and upset the delicate balance of bone remodelling emphasizes the need for all-encompassing management and prevention approaches. In this review, we aim to expose the complexities of corticosteroid-induced bone loss and urge for personalized, proactive measures to improve long-term therapeutic outcomes.

Transcarotid versus transfemoral transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: In the 2021 Transcatheter Valve Therapy (TVT) registry, 8.9 % of patients underwent TAVR via access sites other than the femoral artery. Transthoracic approaches may be contraindicated in some patients and may be associated with poorer outcomes. Therefore other alternative access routes are increasingly being performed. We conducted a systematic review of the literature on transcarotid transcatheter aortic valve replacement (TC-TAVR) and meta-analysis comparing outcomes of TC-TAVR and other access routes. METHODS: We comprehensively searched for controlled randomized and non-randomized studies from 4 online databases. We presented data using risk ratios (95 % confidence intervals) and measured heterogeneity using Higgins' I2. RESULTS: Sixteen observational studies on transcarotid TAVR were included in the analysis; 4 studies compared TC-TAVR vs TF-TAVR. The mean age and STS score for patients undergoing TC-TAVR were 80 years and 7.6 respectively. For TF-TAVR patients, mean age and STS score were 81.2 years and 6.5 respectively. There was no difference between patients undergoing TC-TAVR and TF-TAVR in the following 30-day outcomes: MACE [8.4 % vs 6.7 %; OR 1.32 (95 % CI 0.71-2.46 p = 0.38) I2 = 0 %], mortality [5.6 % vs 4.0 %; OR 0.42 (95 % CI 0.60-3.37, P = 0.42) I2 = 0 %] and stroke [0.7 % vs 2.3 %; OR 0.49 (95 % CI 0.09-2.56, P = 0.40) I2 = 0 %]. There was no difference in 30-day major vascular complications [0.7 % vs 3 %; OR 0.55 (95 % CI 0.06-5.29, P = 0.61) I2 = 39 %], major bleeding [0.7 % vs 3.8 %; OR 0.39 (95 % CI 0.09-1.67, P = 0.21) I2 = 0 %], and moderate or severe aortic valve regurgitation [8.6 % vs 9.9 %; OR 0.89 (95 % CI 0.48-1.65, P = 0.72) I2 = 0 %]. CONCLUSION: There are no significant differences in mortality, stroke MACE and major or life-threatening bleeding or vascular complications when TC-TAVR is compared to TF-TAVR approaches.

Synthesis of N,N'-alkylidene bisamides and Suzuki-Miyaura coupling reaction derivatives with Pd organometallic catalyst anchored to channels of mesoporous silica MCM-41.

At first, an organometallic catalyst namely, Pd-DPyE@MCM-41@MNP was prepared through magnetic (Fe3O4) nanoparticles-doped into channels of mesoporous silica MCM-41 and then, anchoring a novel complex composed of di(4-pyridyl)ethylene and palladium on the inner surface of the support. This immobilized catalyst was successfully identified via VSM, ICP-OES, TEM, FTIR, TGA, SEM, BET, XRD, EDX and elemental mapping analyses. After that, it was used as a versatile, heterogeneous, and magnetically reproducible catalyst in the generation of N,N'-alkylidene bisamides (1a-13a, 8-20 min, 90-98%, 50 °C, solvent-free) and Suzuki-Miyaura coupling (SMC) reaction derivatives (1b-26b, 10-140 min, 86-98%, 60 °C, PEG-400). The VSM plot of Pd-DPyE@MCM-41@MNP displays that this nanocatalyst can be easily recycled by applying an external magnetic field. In both synthetic paths, this nanocatalyst was reused at least seven times without palladium leaching and significantly reducing its catalytic performance. Also, stability and heterogeneous nature of catalyst were approved via ICP-OES technique and hot filtration test.

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study.

AIM: This study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. RESULTS: The average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. CONCLUSION: Metformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

LncRNA NEAT1 in the pathogenesis of liver-related diseases.

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.

Nucleic acid vaccines-based therapy for triple-negative breast cancer: A new paradigm in tumor immunotherapy arena.

Nucleic acid vaccines (NAVs) have the potential to be economical, safe, and efficacious. Furthermore, just the chosen antigen in the pathogen is the target of the immune responses brought on by NAVs. Triple-negative breast cancer (TNBC) treatment shows great promise for nucleic acid-based vaccines, such as DNA (as plasmids) and RNA (as messenger RNA [mRNA]). Moreover, cancer vaccines offer a compelling approach that can elicit targeted and long-lasting immune responses against tumor antigens. Bacterial plasmids that encode antigens and immunostimulatory molecules serve as the foundation for DNA vaccines. In the 1990s, plasmid DNA encoding the influenza A nucleoprotein triggered a protective and targeted cytotoxic T lymphocyte (CTL) response, marking the first instance of DNA vaccine-mediated immunity. Similarly, in vitro transcribed mRNA was first successfully used in animals in 1990. At that point, mice were given an injection of the gene encoding the mRNA sequence, and the researchers saw the production of a protein. We begin this review by summarizing our existing knowledge of NAVs. Next, we addressed NAV delivery, emphasizing the need to increase efficacy in TNBC.

Revolutionizing Infection Control: Harnessing MXene-Based Nanostructures for Versatile Antimicrobial Strategies and Healthcare Advancements.

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare.

A comprehensive review of lncRNA CRNDE in cancer progression and pathology, with a specific glance at the epithelial-mesenchymal transition (EMT) process.

It has been suggested that the long non-coding RNAs (lncRNAs), such as colorectal neoplasia differentially expressed (CRNDE), may contribute to the formation of human cancer. It is yet unknown, though, what therapeutic significance CRNDE expression has for different forms of cancer. CRNDE has recently been proposed as a possible diagnostic biomarker and prognostic pred for excellent specificity and sensitivity in cancer tissues and plasma. To provide the groundwork for potential future therapeutic uses of CRNDE, we briefly overview its biological action and related cancer-related pathways. Next, we mainly address the impact of CRNDE on the epithelial-mesenchymal transition (EMT). The epithelial-mesenchymal transition, or EMT, is an essential biological mechanism involved in the spread of cancer.

Transcarotid versus transthoracic transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Transthoracic approaches may be contraindicated in some patients and may be associated with poorer outcomes. Therefore other alternative access routes are increasingly being performed. We conducted a systematic review of the literature on Transcarotid transcatheter aortic valve replacement (TC-TAVR) and meta-analysis comparing outcomes of TC-TAVR and other access routes. METHODS: We comprehensively searched for controlled randomized and non-randomized studies from 4 online databases. We presented data using risk ratios (95 % confidence intervals) and measured heterogeneity using Higgins' I2. RESULTS: Sixteen observational studies on Transcarotid TAVR were included in the analysis; 4 studies compared 180 TC-TAVR patients vs 524 TT-TAVR patients. The mean age and STS score for patients undergoing TC-TAVR were 80 years and 7.6 respectively. For TT-TAVR patients, the mean age and STS score were 79.7 years and 8.7 respectively. TC-TAVR patients had lower 30-day MACE [7.8 % vs 13.7 %; OR 0.54 (95 % CI 0.29-0.99, P = 0.05)] and major or life-threatening bleeding [4.0 % vs 14.2 %; OR 0.25 (95 % CI 0.09-0.67, P = 0.006)]. There was no significant difference in 30-day: mortality [5.0 % vs 8.6 %; OR 0.61 (95 % CI 0.29-1.30, P = 0.20)], stroke or transient ischemic attack [2.8 % vs 4.0 %; OR 0.65 (95 % CI 0.25-1.73, P = 0.39)] and moderate or severe aortic valve regurgitation [5.0 % vs 4.6 %; OR 1.14. (95 % CI 0.52-2.52, P = 0.75)]. There was a trend towards fewer major vascular complications in TC-TAVR [3.0 % vs 7.8 %; OR 0.42 (95 % CI 0.16-1.12, P = 0.08)]. CONCLUSION: Compared with transthoracic TAVR, TC-TAVR patients had lower odds of 30-day MACE and life-threatening bleeding and no differences in 30-day mortality, stroke or TIA, aortic valve regurgitation.

From knowledge production to knowledge translation: Waterpipe tobacco control research in the Eastern Mediterranean Region.

Waterpipe tobacco smoking (WTS) rates in the Eastern Mediterranean Region (EMR) are the highest worldwide, particularly among young people. Although fiscal policies to curb tobacco use have been recommended by the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC), implementation has been suboptimal. The Eastern Mediterranean Consortium on the Economics of Waterpipe Tobacco Smoking (ECON-WTS) was formed in response to this need to produce knowledge on the economics of WTS in the EMR and apply a comprehensive Knowledge translation (KT) framework. The KT framework comprised priority setting, evidence synthesis, knowledge translation, and knowledge uptake. In this article, we discuss the approaches followed in applying the KT framework to WTS control, providing examples and noting challenges and lessons learned where possible.

Factors associated with intentions to quit tobacco use in Lebanon: A cross-sectional survey.

Introduction: The prevalence of tobacco smoking in Lebanon is among the highest globally. This study aims to determine past attempts to quit smoking among adults and identify factors associated with intentions to quit. Methods: A nationally representative telephone survey was conducted between June and August 2022. Eligibility criteria included people aged >=18 years residing in Lebanon. The questionnaire was divided into three components: socio-demographic characteristics, cigarette and waterpipe tobacco use behaviours. Binary logistic regression was used to examine factors associated with intention to quit cigarette and waterpipe tobacco use. Results: A total of 2003 respondents were included in the study. The prevalence of any tobacco product use was 41%, the prevalence of current cigarette smoking was 41% and the prevalence of current waterpipe tobacco use was 20%. Approximately 24% of adults who smoke cigarettes and 26% of those who use waterpipe tobacco had previous quit attempts mainly due to health concerns. Intentions to quit smoking within the next 6 months were reported among 12% of survey respondents. Among adults who smoke, past quit attempts increased the likelihood of intentions to quit cigarette smoking by 5-fold (OR: 5.11; 95% CI: 1.80-14.47, p = 0.002) and waterpipe tobacco use by 7-fold (OR: 6.98, 95% CI: 2.63-18.51, p = <0.001). Age and income were associated with intentions to quit cigarette but not waterpipe tobacco use. Conclusion: Intention to quit smoking was strongly associated with past quitting attempts. Understanding factors associated with intentions to quit can help inform the development of context specific smoking cessation interventions.

A phenanthroline-based erbium (III) complex: molecular docking, DNA/BSA -binding and biological evaluation.

With the help of both theoretical as well as experimental research, in vitro binding research with CT-DNA (calf thymus) and BSA (bovine serum albumin) were carefully examined to figure out the chemotherapeutic and pharmacokinetic facets of the Erbium complex, which contains 1,10-phenanthroline (Phen). The binding characteristics and the mechanism of complex's interaction with DNA as well as the protein were determined utilizing fluorescence quenching method. Findings indicated that the complex's interaction with DNA via groove binding into DNA's minor grooves, with their binding constants falling within the 104 M-1 range. Furthermore, thermodynamic characteristics and the fluorescence emission of the tryptophan residues of the protein were obtained through fluorescence quenching studies at different temperatures. According to the results of the binding constants, the protein's interactions with the Er- complex were moderate, demonstrating that the compound may be transported effectively by the protein. Molecular docking results supported that of the experimental research. The HeLa and MCF-7 cancer cell lines, along with the normal human fibroblast cell line, were used in an MTT assay evaluation of the Er-complex cytotoxicity. The Er-complex displayed a selective inhibitory effect on the proliferation of different cancer cells.Communicated by Ramaswamy H. Sarma.

Relationship between body mass index and mortality of burns patients: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the relationship between body mass index (BMI) and mortality of burn patients. A comprehensive, systematic search was conducted in different international electronic databases, such as Scopus, PubMed, Web of Science and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as "Body mass index", "Burns" and "Mortality" from the earliest to the April 1, 2023. The quality of the studies included in this systematic review was evaluated using the appraisal tool for cross-sectional studies (AXIS tool). Finally, six articles were included in this systematic review and meta-analysis. A total of 16 154 burn patients participated in six studies. Their mean age was 46.32 (SD = 1.99). Of the participants, 71.7% were males. The mean length of hospitalization was 18.80 (SD = 8.08) days, and the average TBSA in burn patients was 38.32 (SD = 2.79) %. Also, the average BMI in burn patients was 27.10 (SD = 1.75). Results found mortality in patients with abnormal BMI (overweight to morbidity BMI) was 0.19 more than normal BMI (ES: 1.19, 95%CI: 0.76-1.87, Z = 0.75, I2 : 71.8%, p = 0.45). Results of linear dose-response showed each 5 kg/m2 increase in BMI was associated with a 5% increase in mortality that was marginally significant (ES: 1.05, 95%CI: 1.00-1.11, Z = 1.99, I2 : 22.2%, p = 0.047). There was a non-linear relationship between levels of BMI and mortality (Prob > χ2 = 0.02). There was an increase in mortality from percentile 10 to 50, although it was not significant (Correlational coefficient: 0.01, p = 0.85). Also, there was an increase in mortality rate from percentile 50 to 90 that was statistically significant (correlational coefficient: 0.06, p = 0.047). Finally, the results of the study indicated BMI can increase the chance of mortality by 0.19, although it was not significant. As a result, more studies are needed to better judge the relationship between BMI and mortality in burn victims.

Health and economic impacts of introducing specific excise tax to waterpipe tobacco in Egypt: a simulation model of simple and mixed tax policy approaches.

INTRODUCTION: Waterpipe tobacco is taxed at half the rate of cigarettes in Egypt and, unlike cigarettes, does not have a specific excise component. We aimed to simulate the introduction of a specific excise tax on waterpipe tobacco consumption, premature deaths and government waterpipe tobacco revenue in Egypt. METHODS: We took model inputs from the latest available data on consumption, market shares and market share prices, price elasticities of demand, tax structure and from discussions with government officials. We modelled increases to specific excise to produce a 45%, 55%, 65% and 75% tax burden and compared a simple (specific only) structure with a mixed (specific and ad valorem) structure. RESULTS: Under the simple approach, introducing a US$2.1 specific tax would result in a 75% tax burden with 67% fewer waterpipe tobacco units smoked, 1 004 604 averted premature deaths and a 236% increase in government revenue relative to the current tax structure. At the 75% tax burden, the simple approach resulted in 1.5% fewer waterpipe tobacco units consumed, 9000 more averted premature deaths and 12.7% more government revenue compared with the mixed approach. Results for other tax burdens are presented and remained robust to sensitivity analyses. CONCLUSIONS: Introducing a specific excise tax on waterpipe tobacco in Egypt can yield considerable government revenue and public health gains. We recommend the simple approach, in line with the WHO recommendations, which produces greater economic and public health gains than the mixed approach and is easier to administer for the Egyptian government.

Antibacterial activity and DNA interaction of triazine iron and ruthenium complexes: spectroscopic, voltammetric and theoretical studies.

The 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), [Ru(µ-tptz)2]Cl2 and [Fe(µ-tptz)2]Cl2, complexes containing Ru (1) and Fe (2) are created. Using electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, viscosity measurement and electrochemistry, as well as two complexes with Fish Salmon DNA (FS-DNA), the binding interactions of these complexes were investigated. According to binding assays, complexes bind to DNA through a mild intercalation mechanism, most likely via the DNA helix's base pairs being intercalated by the tptz ligand. Additionally, complex (2) is more capable of binding than complex (1). The electrochemical method offers a quick and easy way to determine the binding constant (Kb). The antibacterial performance of these complexes versus Gram-positive and Gram-negative bacteria was examined using the zone of inhibition test, MIC, and MBC method, and the results revealed that complex (2) exhibits strong antibacterial activity against these bacteria. The outcomes of this investigation will help in understanding DNA interaction mechanisms as well as the creation of a prospective one. Additionally, the density functional theory (DFT) computation included probes of DNA structure and conformation as well as potential pharmacological regulators for particular disorders to fully explain the experimental results.

Workforce diversity in specialist physicians: Implications of findings for religious affiliation in Anaesthesia & Intensive Care.

BACKGROUND: Minority ethnic identification between physician and patient can reduce communication and access barriers, improve physician-patient relationship, trust, and health outcomes. Religion influences health beliefs, behaviours, treatment decisions, and outcomes. Ethically contentious dilemmas in treatment decisions are often entangled with religious beliefs. They feature more in medical specialties such as Anaesthesia & Intensive Care, with issues including informed consent for surgery, organ donation, transplant, transfusion, and end-of-life decisions. METHODS: We investigate diversity in religious affiliation in the UK medical workforce, using data from the General Medical Council (GMC) specialist register and Health Education England (HEE) trainee applications to medical specialties. We performed conservative Bonferroni corrections for multiple comparisons using Chi-squared tests, as well as normalised mutual-information scores. Robust associations that persisted on all sensitivity analyses are reported, investigating whether ethnicity or foreign primary medical qualification could explain the underlying association. FINDINGS: The only significant and robust association in both GMC and HEE datasets affecting the same religious group and specialty was disproportionately fewer Anaesthesia & Intensive Care physicians with a religious affiliation of "Muslim", both as consultants (RR 0.57[0.47,0.7]) and trainee applicants (RR 0.27[0.19,0.38]. Associations were not explained by ethnicity or foreign training. We discuss the myriad of implications of the findings for multi-cultural societies. CONCLUSIONS: Lack of physician workforce diversity has far-reaching consequences, especially for specialties such as Anaesthesia and Intensive Care, where ethically contentious decisions could have a big impact. Religious beliefs and practices, or lack thereof, may have unmeasured influences on clinical decisions and on whether patients identify with physicians, which in turn can affect health outcomes. Examining an influencing variable such as religion in healthcare decisions should be prioritised, especially considering findings from the clinician-patient concordance literature. It is important to further explore potential historical and socio-cultural barriers to entry of training medics into under-represented specialties, such as Anaesthesia and Intensive Care.

Synthesis of a novel Cu/DPA-MOF/OP/CS hydrogel with high capability in antimicrobial studies.

Today, with the indiscriminate use of antibiotics, we face the resistance of some bacterial strains against some antibiotics. Therefore, it is essential to report and synthesize new compounds with antimicrobial properties. A novel copper/dipicolinic acid-metal-organic framework cross-linked oxidized pectin and chitosan (Cu/DPA-MOF/OP/CS) hydrogel polymer was synthesized under environmental conditions with the controllable process, which uses biodegradable polymer compounds such as pectin and chitosan in its structure. The efficient physicochemical features of the synthesized Cu/DPA-MOF/OP/CS hydrogel using SEM, FT-IR, TGA, BET, XRD, and EDS/mapping were identified and confirmed. The newly synthesized Cu/DPA-MOF/OP/CS hydrogel showed activity against Gram-positive and Gram-negative bacterial strains and fungal species, and significant antibacterial and antifungal properties were observed. In antibacterial activity, the MIC against Gram-positive species was in the range of 16-128 mg/mL, the MIC against Gram-negative species was in the range of 64-256 mg/mL, and the MIC against fungal species was in the range of 128-512 mg/mL. In antimicrobial evaluations, in addition to the MIC test, the MBC test, the MFC test, and the IZD test were performed, and the results were reported. The results were compared with commercial antibiotics in the market. Development of novel nanostructures based on hydrogel polymers with distinctive functionality can affect the performance of these nanostructures in different areas.

The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.

Glycolysis in human cancers: Emphasis circRNA/glycolysis axis and nanoparticles in glycolysis regulation in cancer therapy.

The metabolism of cancer has been an interesting hallmark and metabolic reprogramming, especially the change from oxidative phosphorylation in mitochondria to glucose metabolism known as glycolysis occurs in cancer. The molecular profile of glycolysis, related molecular pathways and enzymes involved in this mechanism such as hexokinase have been fully understood. The glycolysis inhibition can significantly decrease tumorigenesis. On the other hand, circRNAs are new emerging non-coding RNA (ncRNA) molecules with potential biological functions and aberrant expression in cancer cells which have received high attention in recent years. CircRNAs have a unique covalently closed loop structure which makes them highly stable and reliable biomarkers in cancer. CircRNAs are regulators of molecular mechanisms including glycolysis. The enzymes involved in the glycolysis mechanism such as hexokinase are regulated by circRNAs to modulate tumor progression. Induction of glycolysis by circRNAs can significantly increase proliferation rate of cancer cells given access to energy and enhance metastasis. CircRNAs regulating glycolysis can influence drug resistance in cancers because of theirimpact on malignancy of tumor cells upon glycolysis induction. TRIM44, CDCA3, SKA2 and ROCK1 are among the downstream targets of circRNAs in regulating glycolysis in cancer. Additionally, microRNAs are key regulators of glycolysis mechanism in cancer cells and can affect related molecular pathways and enzymes. CircRNAs sponge miRNAs to regulate glycolysis as a main upstream mediator. Moreover, nanoparticles have been emerged as new tools in tumorigenesis suppression and in addition to drug and gene delivery, then mediate cancer immunotherapy and can be used for vaccine development. The nanoparticles can delivery circRNAs in cancer therapy and they are promising candidates in regulation of glycolysis, its suppression and inhibition of related pathways such as HIF-1α. The stimuli-responsive nanoparticles and ligand-functionalized ones have been developed for selective targeting of glycolysis and cancer cells, and mediating carcinogenesis inhibition.

The Probiotic Lactobacillus sakei Subsp. Sakei and Hawthorn Extract Supplements Improved Growth Performance, Digestive Enzymes, Immunity, and Resistance to the Pesticide Acetamiprid in Common Carp (Cyprinus carpio).

This study evaluated the impacts of the probiotic, Lactobacillus sakei (L. sakei), and the extract of hawthorn, Crataegus elbursensis, on growth and immunity of the common carp exposed to acetamiprid. Fish (mean ± SE: 11.48 ± 0.1 g) feeding was done with formulated diets (T 1 (control): no supplementation, T 2: 1 × 106 CFU/g LS (Lactobacillus sakei), T3: 1 × 108 CFU/g LS, T 4: 0.5% hawthorn extract (HWE), and T 5: 1% HWE) for 60 days and then exposed to acetamiprid for 14 days. The growth performance improved in the fish fed LS at dietary level of 1 × 108 CFU/g, even after exposure to acetamiprid (P < 0.05). Intestinal Lactobacillus sakei (CFU/g) load increased (P < 0.05), following supplementation with the probiotic-enriched diet. The LS-treated fish had increases in the activity of digestive enzymes (P < 0.05). Both LS and HWE stimulated antioxidant enzymes and immune system components in serum and mucus (alkaline phosphatase (ALP), protease, total Ig, and lysozyme) (P < 0.05). However, the changes were different depending on the kind of the supplement. The malondialdehyde (MDA) levels decreased in HWE-treated fish after acetamiprid exposure (P < 0.05). Both LS and HWE reduced the liver metabolic enzymes (LDH, ALP, AST, ALT, and LDH) in serum both before and after exposure to the pesticide (P < 0.05). However, each enzyme exhibited a different change trend depending on the type of the supplement. HWE showed a stress-ameliorating effect, as glucose and cortisol levels declined in the HWE-treated fish (P < 0.05). This study indicated the immunomodulatory impacts of LS (1 × 108 CFU/g) and HWE (at dietary levels of 0.5-1%). The probiotic showed more performance compared to HWE. However, the HWE mitigated oxidative stress more efficiently than the probiotic.