Volitionally regulated breathing with prolonged expiration influences food craving and impulsivity.

Introduction Previously an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration ratio (i/e) also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons. Methods Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M: F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) (bpm) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M: F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during and after breathing intervention (or control) (standard limb lead I, acquisition at 2000 Hz, with a LF filter = 0.5 Hz and HF filter = 50 Hz. Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, hunger and satiety were recorded before and after the intervention/control. Results The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p<0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states. Conclusion Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both.

Muscle strength and body composition in obese adults following nine months of yoga or nutrition advice: A comparative controlled trial.

INTRODUCTION: Muscle strength is impaired in obese persons due to low physical activity, obesity-related modifications in muscle morphology and as a consequence of calorie regulation (where applicable). Previously decreased BMI and increased hand grip strength was reported following a short duration yoga intervention in obese adults. METHODS: The present comparative controlled study was conducted on two hundred and ninety seven obese adults (BMI ≥25 Kg/M2) aged between 20 and 59 years, to determine the effects of nine months of yoga or nutrition advice on muscle strength and body composition. Participants were assessed for bilateral hand grip strength, leg and back strength, and body composition at baseline, after 3 months, 6 months and 9 months of yoga or nutrition advice. BMI-adjusted bilateral hand grip strength and leg and back strength were calculated. RESULTS: In the linear mixed model analyses, there was a significant interaction effect of Time X Groups for (i) right hand grip strength (F3,668.465 = 9.297, p < 0.001), (ii) left hand grip strength (F3,673.408 = 14.469, p < 0.001), (iii) BMI-adjusted right hand grip strength (F3,650.542 = 9.954, p < 0.001) and (iv) BMI-adjusted left hand grip strength (F3,655.518 = 13.853, p < 0.001). Bonferroni corrected post-hoc analyses (padj < 0.05; in all cases) showed a significant increase in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the yoga group while a decrease in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the nutrition advice group. CONCLUSION: Yoga practice appears to protect and increase upper limb muscle strength in obese adults.

Traditional Nostril Yoga Breathing Practices and Oxygen Consumption: A Randomized, Cross-over Study.

Background: Traditional yoga texts describe "cross nostril breathing," with inhalation and exhalation through different nostrils. Previous research reported no clear differences in oxygen consumption during uninostril breathing (i.e., inhalation and exhalation through the same nostril), hence not supporting right and left uninostril breathing as activating or relaxing, respectively, with no research on oxygen consumed in "cross nostril breathing." Methods: Oxygen consumed during "cross nostril breathing" was measured in healthy participants (n = 47, males, 26.3 ± 6.4 years). Five sessions (viz., right nostril inspiration yoga breathing [RNIYB], left nostril inspiration yoga breathing [LNIYB], alternate nostril yoga breathing [ANYB], breath awareness (BAW), and quiet rest (QR) were conducted on separate days in random order. Sessions were 33 min in duration with pre, during, and post states. Results: Volume of oxygen consumed (VO2) and carbon dioxide eliminated (VCO2) increased during RNIYB (9.60% in VO2 and 23.52% in VCO2), LNIYB (9.42% in VO2 and 21.20% in VCO2) and ANYB (10.25% in VO2 and 22.72% in VCO2) with no significant change in BAW and QR. Diastolic blood pressure decreased during BAW and QR and after all five sessions (P < 0.05; in all cases). All comparisons were with the respective preceding state. Conclusion: During the three yoga breathing practices, the volume of oxygen consumed increased irrespective of the nostril breathed through, possibly associated with (i) conscious regulation of the breath; (ii) attention directed to the breath, and (iii) "respiration-locked cortical activation." Restriction of the study to males reduces the generalizability of the findings.

Cerebral Hemodynamics and Vagally Mediated HRV Associated with High- and Low-frequency Yoga Breathing: An Exploratory, Randomized, Crossover Study.

Background: Volitionally modifying respiration leads to changes in middle cerebral arterial (MCA) blood flow. The effect of changes in breath rate on MCA blood flow has not been reported. Aims and Objectives: To determine the effect of slow (bumblebee yoga breathing) and fast (high frequency yoga breathing) yoga breathing techniques on MCA blood flow and vagally mediated heart rate variability. Materials and Methods: Thirty participants (mean age ± standard deviation, 27.3 ± 4.2 years) were assessed on 2 separate days practicing either high frequency yoga breathing (HFYB, breath frequency 54.2/min) or slow frequency bumblebee yoga breathing (BBYB, breath frequency 3.8/min) in random order to determine the effects of changes in breath frequency on MCA hemodynamics. Assessments included transcranial Doppler sonography, vagally mediated heart rate variability (VmHRV), and respiration. Results: Both HFYB and BBYB (i) reduced MCA flow velocities, i.e., peak systolic, end diastolic, and mean flow velocities, and (ii) increased MCA pulsatility indices. There was an increase in VmHRV during BBYB based on increased power in high frequency (HF) and low frequency (LF). LF reflects VmHRV for slow breath frequencies. In BBYB the average breath rate was 3.8 breaths/min. In contrast, VmHRV decreased during HFYB (based on reduced HF power; repeated measures analysis of variance, P < 0.05, all cases). Conclusion: Hence, irrespective of the differences in breath frequency, both HFYB and BBYB appear to reduce MCA flow velocities and increase the resistance to blood flow bilaterally, although the VmHRV changed in opposite directions. MCA velocity and pulsatility changes are speculated to be associated with low global neural activity during yoga breathing.

Ferroptosis and circular RNAs: new horizons in cancer therapy.

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance.

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.

Fecal microbiome extract downregulates the expression of key proteins at the interface between airway remodelling and lung cancer pathogenesis in vitro.

Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.

Computational and biological approaches in repurposing ribavirin for lung cancer treatment: Unveiling antitumorigenic strategies.

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.

Treatment avenues for age-related macular degeneration: Breakthroughs and bottlenecks.

Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Exploring the complex interplay between Parkinson's disease and BAG proteins.

Parkinsons disease (PD) is a chronic fast growing neurodegenerative disorder of Central Nervous System (CNS) characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and formation of Lewy bodies (LBs) which causes dopamine deficiency within basal ganglia leading to motor and non-motor manifestation. According to reports, many factors are responsible for pathogenesis of PD which includes environmental factors, genetic factors, and aging factors. Whereas death of dopaminergic neurons is also caused by oxidative stress, neuroinflammation, and autophagy disorder. Molecular chaperones/co-chaperones are proteins that binds to an unstable conformer of another protein and stabilizes it. Chaperones prevent incorrect interaction between non-native polypeptides which increases the yield but not the rate of reaction. The Bcl-2-associated athanogene (BAG) is a multifunctional group of proteins belonging to BAG family of co-chaperones. Recent studies demonstrates that chaperones interact with PD-related proteins. Co-chaperones like BAG family proteins regulate the function of chaperones. Molecular chaperones regulate the mitochondrial functions by interacting with the PD-related proteins associated with it. This review studies the contribution of chaperones and PD-related proteins in pathogenesis of PD aiming to provide an alternate molecular target for preventing the disease progression.

Exploring the role of the ocular surface in the lung-eye axis: Insights into respiratory disease pathogenesis.

Chronic respiratory diseases (CRDs) represent a significant proportion of global health burden, with a wide spectrum of varying, heterogenic conditions largely affecting the pulmonary system. Recent advances in immunology and respiratory biology have highlighted the systemic impact of these diseases, notably through the elucidation of the lung-eye axis. The current review focusses on understanding the pivotal role of the lung-eye axis in the pathogenesis and progression of chronic respiratory infections and diseases. Existing literature published on the immunological crosstalk between the eye and the lung has been reviewed. The various roles of the ocular microbiome in lung health are also explored, examining the eye as a gateway for respiratory virus transmission, and assessing the impact of environmental irritants on both ocular and respiratory systems. This novel concept emphasizes a bidirectional relationship between respiratory and ocular health, suggesting that respiratory diseases may influence ocular conditions and vice versa, whereby this conception provides a comprehensive framework for understanding the intricate axis connecting both respiratory and ocular health. These aspects underscore the need for an integrative approach in the management of chronic respiratory diseases. Future research should further elucidate the in-depth molecular mechanisms affecting this axis which would pave the path for novel diagnostics and effective therapeutic strategies.

Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead.

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.

Patterns, barriers, and utilization of oral healthcare provided at primary health centers (PHCs) and its association with oral health status among rural population in Rohtak district, Haryana: A household cross-sectional study.

Introduction: Access to oral healthcare is limited in rural areas, resulting in disparities in oral health services. Primary health centers (PHCs) are essential for providing integrated oral healthcare to rural populations. This study examines the patterns, barriers, and utilization of oral healthcare at PHCs in Rohtak district, Haryana. Materials and Methods: In this 6-month household cross-sectional study, data were collected from a sample of 600 participants residing in rural areas under the jurisdiction of three randomly selected PHCs in Rohtak district. The study employed multistage cluster systematic random sampling procedures. Data collection included structured questionnaires and clinical oral examinations following the type-III ADA classification. Participants' oral health status was evaluated using the WHO oral health assessment form for adults (2013). Descriptive and analytical statistics were used for data analysis. Results and Discussion: Dental caries and periodontal diseases were more common in older age groups. Barriers to oral healthcare among the elderly include fear of dental procedures and low dental literacy. Proximity to PHCs influenced dental service utilization, with higher rates among participants living near a PHC, that is, within 5 km of a PHC. Conclusion: Age, gender, proximity to PHCs, household size, and socioeconomic status play crucial roles in the utilization of oral health services among the rural population. Addressing these factors is essential for improving oral healthcare and overcoming barriers. It is crucial to enhance the accessibility, affordability, and availability of oral health services at PHCs to promote better oral health and overall well-being in rural areas.

Transcriptome-wide association mapping provides insights into the genetic basis and candidate genes governing flowering, maturity and seed weight in rice bean (Vigna umbellata).

BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.

PermDroid a framework developed using proposed feature selection approach and machine learning techniques for Android malware detection.

The challenge of developing an Android malware detection framework that can identify malware in real-world apps is difficult for academicians and researchers. The vulnerability lies in the permission model of Android. Therefore, it has attracted the attention of various researchers to develop an Android malware detection model using permission or a set of permissions. Academicians and researchers have used all extracted features in previous studies, resulting in overburdening while creating malware detection models. But, the effectiveness of the machine learning model depends on the relevant features, which help in reducing the value of misclassification errors and have excellent discriminative power. A feature selection framework is proposed in this research paper that helps in selecting the relevant features. In the first stage of the proposed framework, t-test, and univariate logistic regression are implemented on our collected feature data set to classify their capacity for detecting malware. Multivariate linear regression stepwise forward selection and correlation analysis are implemented in the second stage to evaluate the correctness of the features selected in the first stage. Furthermore, the resulting features are used as input in the development of malware detection models using three ensemble methods and a neural network with six different machine-learning algorithms. The developed models' performance is compared using two performance parameters: F-measure and Accuracy. The experiment is performed by using half a million different Android apps. The empirical findings reveal that malware detection model developed using features selected by implementing proposed feature selection framework achieved higher detection rate as compared to the model developed using all extracted features data set. Further, when compared to previously developed frameworks or methodologies, the experimental results indicates that model developed in this study achieved an accuracy of 98.8%.

Non-coding RNA mediated regulation of PI3K/Akt pathway in hepatocellular carcinoma: Therapeutic perspectives.

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

PSPC1 Binds to HCV IRES and Prevents Ribosomal Protein S5 Binding, Inhibiting Viral RNA Translation.

Hepatitis C virus (HCV) infects the human liver, and its chronic infection is one of the major causes of Hepatocellular carcinoma. Translation of HCV RNA is mediated by an Internal Ribosome Entry Site (IRES) element located in the 5'UTR of viral RNA. Several RNA Binding proteins of the host interact with the HCV IRES and modulate its function. Here, we demonstrate that PSPC1 (Paraspeckle Component 1), an essential paraspeckle component, upon HCV infection is relocalized and interacts with HCV IRES to prevent viral RNA translation. Competition UV-crosslinking experiments showed that PSPC1 interacts explicitly with the SLIV region of the HCV IRES, which is known to play a vital role in ribosomal loading to the HCV IRES via interaction with Ribosomal protein S5 (RPS5). Partial silencing of PSPC1 increased viral RNA translation and, consequently, HCV replication, suggesting a negative regulation by PSPC1. Interestingly, the silencing of PSPC1 protein leads to an increased interaction of RPS5 at the SLIV region, leading to an overall increase in the viral RNA in polysomes. Overall, our results showed how the host counters viral infection by relocalizing nuclear protein to the cytoplasm as a survival strategy.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.