Normal Liver Research Articles

Prevalence and characterization of pain in radiation oncology: the PREDORT multicenter cross-sectional study.

Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services. A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent. Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p < 0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p = 0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p < 0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%). The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.

Resection and postoperative pazopanib for intraspinal recurrent solitary fibrous tumor: illustrative case.

Intracranial solitary fibrous tumors (SFTs) rarely recur in the spinal space. Only 4 cases of spinal recurrence from intracranial SFT have been reported; therefore, the optimal treatment of recurrent spinal SFT remains unclear. A 53-year-old woman with a history of resection of a right occipital anaplastic SFT presented with progressive back and side pain. She was diagnosed with an intradural extramedullary tumor ventral to the spinal cord at the T5-7 level. She underwent tumor resection with T5-6 laminectomy and T4 and T7 partial laminectomy. The tumor was completely removed in a piecemeal fashion using an ultrasonic aspirator with careful control of bleeding. Her symptoms quickly improved after the surgery, and she returned to normal life. The tumor was diagnosed as SFT. Pazopanib was administered postoperatively. Despite the recurrence of the intracranial tumor, the patient was alive without recurrence of the spinal tumor 14 months after resection. Although rare, intracranial SFTs have a risk of spinal recurrence. Complete resection of a recurrent spinal SFT can be achieved even in the ventral location. Pazopanib could be a possible therapeutic option for preventing local tumor recurrence in the management of recurrent spinal SFT. https://thejns.org/doi/10.3171/CASE24217.

Morin Prevents Non-Alcoholic Hepatic Steatosis in Obese Rats by Targeting the Peroxisome Proliferator-Activated Receptor Alpha (PPARα).

Obesity has become a widespread issue globally. Morin, a flavonoid with traditional use in managing hyperglycemia and hyperlipidemia, has demonstrated antioxidant and anti-inflammatory properties in experimental studies. This research aims to explore the anti-obesity potential of morin in rats subjected to a high-fat diet (HFD) and investigate whether its effects are mediated through PPARα regulation. Young adult male Wistar albino rats were divided into four groups (n = 8/group): normal, morin (50 mg/kg/BWT, oral), HFD, and HFD + morin (50 mg/kg/BWT, oral). Treatments were administered daily for 17 consecutive weeks. Morin mitigated the elevation in glucose levels and decreased fasting glucose and insulin levels, along with the HOMA-IR index, in HFD-fed rats. Furthermore, morin reduced calorie intake, final body weights, and the masses of subcutaneous, epididymal, peritoneal, and mesenteric fat in these rats. It also attenuated the rise in systolic blood pressure in HFD-fed rats and decreased serum levels of triglycerides, cholesterol, free fatty acids, LDL-c, and leptin, while increasing levels of HDL-c and adiponectin in both normal and HFD-fed rats. Moreover, morin restored normal liver structure and reduced fat vacuole accumulation in HFD-fed rats. Notably, it upregulated mRNA levels of PPARα in the livers and white adipose tissue of both normal and HFD-fed rats. These findings suggest the potential use of morin to enhance fatty acid oxidation in white adipose tissue and mitigate obesity, warranting further clinical investigation into its therapeutic applications.

Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.

The endoplasmic reticulum (ER) is indispensable for maintaining normal life activities. Dysregulation of the ER function results in the accumulation of harmful proteins and lipids and the disruption of intracellular signaling pathways, leading to cellular dysfunction and eventual death. Protein misfolding within the ER disrupts its delicate balance, resulting in the accumulation of misfolded or unfolded proteins, a condition known as endoplasmic reticulum stress (ERS). Renal fibrosis, characterized by the aberrant proliferation of fibrotic tissue in the renal interstitium, stands as a grave consequence of numerous kidney disorders, precipitating a gradual decline in renal function. Renal fibrosis is a serious complication of many kidney conditions and is characterized by the overgrowth of fibrotic tissue in the glomerular and tubular interstitium, leading to the progressive failure of renal function. Studies have shown that, during the onset and progression of kidney disease, ERS causes various problems in the kidneys, a process that can lead to kidney fibrosis. This article elucidates the underlying intracellular signaling pathways modulated by ERS, delineating its role in triggering diverse forms of cell death. Additionally, it comprehensively explores a spectrum of potential pharmacological agents and molecular interventions aimed at mitigating ERS, thereby charting novel research avenues and therapeutic advancements in the management of renal fibrosis.

Advances in tacrine for Alzheimers disease

Alzheimers disease is a kind of neurodegenerative disease with insidious and progressive onset, which will affect the normal life of patients to varying degrees. At present, there is no specific drug that can completely cure Alzheimers disease, and there is still a long way to go in the treatment of the disease. In order to provide better ideas for the development of drugs to treat Alzheimers disease, people have speculated and verified a variety of pathogenesis of the disease as far as possible and developed targeted drugs on this basis. In addition to the need to develop drugs from multiple pathogenetic perspectives, it is also necessary to conduct longitudinal studies on one drug. Since tachrine is one of the drugs with great development potential, this paper will take Tachrine, a representative of cholinesterase inhibitors, as the main drug research object, analyze the structure and efficacy of various existing tachrine drugs, and try to provide the future development direction of Tachrine drug transformation.

Alterations of the Fatty Acid Profile and the Expression of Genes Related to FA Metabolism in Cirrhotic Liver Tissue.

In addition to direct damage to hepatocytes, long-term ethanol consumption leads to lipid accumulation and hepatic steatosis, as well as to the dysregulation of lipid metabolism. The final step in various liver diseases is cirrhosis. The aim of this study was to compare the FA (fatty acids) profile and expression levels of genes involved in lipid metabolism in cirrhotic liver tissue and normal liver tissue. Exploring the changes in the FA profile and expression of genes related to fatty acid metabolism in cirrhotic liver tissue reveals a molecular landscape that goes beyond the surface of traditional liver function assessments. Understanding the shifts in gene expression and fatty acid composition in liver tissue opens avenues for interventions that may aid in the treatment of cirrhosis in the future.

Creating a sense of intangible science: Making it understandable to a broad public via geoheritage

The methods and result of scientific studies are often difficult to understand for non-specialists due to their esoteric nature. Such lack of understanding means that such work is removed from our normal life experience, and thus, the applicability, interest and use of such work can be minimal. The communication of geoscience finds a natural conduit through geoheritage. A good example of an inaccessible technique far removed from everyday experience is anisotropy of magnetic susceptibility (AMS), an extremely useful geoscience technique with many applications, including finding strain and flow directions in rocks. We explored here how to make “AMS” understandable, using three different volcanic sites where the flow of molten rock is an important aspect, each situated in different types of geoheritage visitation context (wild trekkers, beach visitors, and walkers). The method we developed and tested follows the production of simple and adapted explanations, and is coupled with geoheritage inventorying and communication. We utilized the tangible geological features of outcrops, as well as intangible elements such as rock magnetic data, and conducted a geoheritage inventory using the modified geosite assessment model (M-GAM) to create narratives for popular comprehension. The M-GAM analysis has identified the geosites of the San Bartolo lava flow of the Stromboli volcano for the communication of AMS. Later, a simple and comprehensible definition of AMS and thus of the flow processes was created using a step-by-step process. This method could be useful for scientific studies to allow them to reach out to a wider public, using their input in the simple explanation stage to con-construct a narrative. This would provide a way for science to be more widely appreciated, useful and applicable.

The COVID-19-Led Reverse Migration and Labour Supply in Rural Economy: Challenges, Opportunities and Road Ahead in Chhattisgarh

Migration is an integral part of the Indian economy and constitutes a significant share in the GDP of the country. But the COVID-19 pandemic has emerged as a devastating shock resulting in huge reverse migration in India as well as in its respective states. In this context the present study tries to investigate labour supply and employment opportunity in rural areas of Chhattisgarh due to COVID-19-led reverse migration and also examines the gender specific impacts of COVID-19 on reverse migrants in Chhattisgarh. The study also suggests the possible measures to rebuild the Chhattisgarh’s rural economy after COVID-19. Thus, the study inculcates both secondary and primary data. Descriptive statistics and regression analysis are computed to get the results. The study found that there is a sudden rise in labour supply in the rural economy of Chhattisgarh. Job loss is the biggest problem faced by migrants followed by loss in income. The study also found that there is no significant impact of reverse migration due to Covid-19 between both the gender in rural Chhattisgarh. Thus, on the basis of primary survey and focused group discussions the study concludes that the returned migrants would surely get back to their normal lives and would gradually afford the better standard of living to themselves as well as to their families. A comprehensive overview of the economic, health and gendered implications of the Covid-19 pandemic reveals the need for a more proactive and on-the-ground strategy to combat the post -crisis scenario in the rural economy of Chhattisgarh. Also, the Covid-19 pandemic have reinforced the need for and the importance of compiling data of migrants. Such a database helps in effective administration of various government interventions. However, there is also an urgent call for the proactive actions to be undertaken to retain these reverse migrants in their original source, so that they would contribute towards the development of their own state.

Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acid‒base homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.

An expert opinion on rescuing atypically pronucleated human zygotes by molecular genetic fertilization checks in IVF.

IVF laboratories routinely adopt morphological pronuclear assessment at the zygote stage to identify abnormally fertilized embryos deemed unsuitable for clinical use. In essence, this is a pseudo-genetic test for ploidy motivated by the notion that biparental diploidy is required for normal human life and abnormal ploidy will lead to either failed implantation, miscarriage, or significant pregnancy complications, including molar pregnancy and chorionic carcinoma. Here, we review the literature associated with ploidy assessment of human embryos derived from zygotes displaying a pronuclear configuration other than the canonical two, and the related pregnancy outcome following transfer. We highlight that pronuclear assessment, although associated with aberrant ploidy outcomes, has a low specificity in the prediction of abnormal ploidy status in the developing embryo, while embryos deemed abnormally fertilized can yield healthy pregnancies. Therefore, this universal strategy of pronuclear assessment invariably leads to incorrect classification of over 50% of blastocysts derived from atypically pronucleated zygotes, and the systematic disposal of potentially viable embryos in IVF. To overcome this limitation of current practice, we discuss the new preimplantation genetic testing technologies that enable accurate identification of the ploidy status of preimplantation embryos and suggest a progress from morphology-based checks to molecular fertilization check as the new gold standard. This alternative molecular fertilization checking represents a possible non-incremental and controversy-free improvement to live birth rates in IVF as it adds to the pool of viable embryos available for transfer. This is especially important for the purposes of 'family building' or for poor-prognosis IVF patients where embryo numbers are often limited.

Effects of Aromatherapy on Physical and Psychological Symptoms in Cancer Patients: A Systematic Review and Meta-analysis.

Numerous physical and psychological symptoms experienced by cancer patients seriously affect their normal lives. Many academics and medical professionals have attempted to use aromatherapy in this situation to help cancer patients manage their physical and emotional problems. To systematically investigate the efficacy of aromatherapy on physical and psychological symptoms in cancer patients. A systematic review and meta-analysis of randomized controlled trials was performed. Four electronic databases were searched. The review process followed a registered priori review protocol and was reported using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Data extraction and quality assessment were performed in parallel. Twenty-six studies with 2912 subjects were included. Meta-analysis showed that aromatherapy significantly improved sleep quality, fatigue, anxiety, and depression. We performed a subgroup analysis according to the different plant or animal aromatics contained in the oil, which found that lavender oil significantly reduced preoperative anxiety. In addition, aromatherapy massage was superior to inhaled aromatherapy in reducing anxiety. Moreover, cancer patients who used aromatherapy reduced the frequency of vomiting in 24 hours. Aromatherapy is a useful treatment for improving sleep quality and reducing symptoms of fatigue, anxiety, and depression in cancer patients, as well as the frequency of vomiting over 24 hours. Healthcare providers can use aromatherapy to alleviate psychological and physical symptoms in cancer patients. The use of lavender oil and massage is recommended in clinical settings to improve anxiety symptoms in cancer patients.

Optimizing of a suitable protocol for isolating tissue-derived extracellular vesicles and profiling small RNA patterns in hepatocellular carcinoma.

Extracellular vesicles (EVs) facilitate cell-cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive. To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis. A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9+ and CD63+ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895-1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming. The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.

Driving Forces of Impunity in South Asia: A Human Rights Framework

This paper is the outcome of a research on impunity in South Asia. Undertaken by Forum Asia in 2021, the research collected cases from Afghanistan, Bangladesh, India, Maldives, Nepal, Pakistan and Sri Lanka. The cases related to impunity were collected by the country researchers deputed in these countries. The lead author and co-author of this paper were the main contributors in compiling the country reports, processing the data, editing them and publishing them as country reports and South Asia regional report. Out of the huge compilation, this paper mainly sketches the debates over the constructs on impunity prevailing in these countries. The paper highlights how these countries are combating impunity with respect to the drivers and to what extent this effort is compatible in the realm of global human rights framework. Impunity is found deeply rooted in South Asia both in the cognitive, productive, economic, and political lives of the victims as well as on the psychosocial mindset of society. Individual victims of gross violations of human rights have been denied access to justice at large. This develops post-traumatic stress disorder (PTSD) along with loss of memory, nightmares, excessive fear, loss of attention, loss of self-esteem, self-isolation, distrust, withdrawal from normal life events as well as a refusal to participate in civil, cultural and social interactions. The paper concludes that most South Asian states follow democratic norms and values as they hold periodic elections and form governments. These states, however, severely lack concrete plans and tools to combat impunity. The paper suggests the vibrant role of the legislation penal codes in these countries to make accountable to the stakeholders involved in impunity matters both as perpetrators and those acting against the perpetrators.

Viral Rebound After Antiviral Treatment: A Mathematical Modeling Study of the Role of Antiviral Mechanism of Action.

The development of antiviral treatments for SARS-CoV-2 was an important turning point for the pandemic. Availability of safe and effective antivirals has allowed people to return back to normal life. While SARS-CoV-2 antivirals are highly effective at preventing severe disease, there have been concerning reports of viral rebound in some patients after cessation of antiviral treatment. In this study, we use a mathematical model of viral infection to study the potential of different antivirals to prevent viral rebound. We find that antivirals that block production are most likely to result in viral rebound if the treatment time course is not sufficiently long. Since these antivirals do not prevent infection of cells, cells continue to be infected during treatment. When treatment is stopped, the infected cells will begin producing virus at the usual rate. Antivirals that prevent infection of cells are less likely to result in viral rebound since cells are not being infected during treatment. This study highlights the role of antiviral mechanism of action in increasing or reducing the probability of viral rebound.

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver.Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco’s Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-β, Homeostasis model assessment of β-cell function; IL-1β, Interleukin-1β; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.

Calenduloside E inhibits hepatocellular carcinoma cell proliferation and migration by down-regulating GPX4 and SLC7A11 expression through the autophagy pathway

To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma (HCC) cell proliferation and migration. HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4, SLC7A11, LC3, P62 and phosphorylation of Akt/mTOR using Western blotting. The effects LY294002 and Rapamycin (the inhibitor and activator of autophagy, respectively) on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays. The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes. GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting. Calenduloside E obviously inhibited the viability of HCC cells. GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines, and their expression levels were negatively correlated with the patients'survival. In HCC cell lines, calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins, activated the Akt-mTOR pathway, and enhanced the expression of LC3 Ⅱ. The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002. Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells, while activating this pathway produced the opposite effect. Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Sodium butyrate and sorafenib synergistically inhibit hepatocellular carcinoma cells possibly by inducing ferroptosis through inhibiting YAP

To investigate whether sodium butyrate (NaB) and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms. CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib, alone or in combination, on proliferation of HepG2 cells, and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe. TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues. The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting. NaB (2 mmol/L) significantly reduced the IC50 of sorafenib in HepG2 cells, and combination index analysis confirmed the synergy between sorafenib and NaB. The ferroptosis inhibitor Fer-1 and the YAP activator (XMU) obviously reversed the growthinhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells. The combined treatment with NaB and sorafenib, as compared with the two agents used alone, significantly inhibited colony formation of HepG2 cells, further enhanced cellular shrinkage and dispersion, and decreased intracellular GSH and lipid ROS levels, and these effects were reversed by Fer-1 and XMU. TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues. NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells. NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.

COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few. Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children. We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports. The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives. COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.

Detecting Hepatic Steatosis Among Potential Liver Donors by Using Non-Invasive Methods

Objective: To evaluate the effectiveness of non-invasive methods in detecting hepatic steatosis among potential liver donors. Methodology: This cross-sectional descriptive study included 67 potential liver donors, recruited via consecutive non-probability sampling over a two-year period (2021-2023). Data collection involved a semi-structured questionnaire covering demographics and biochemical indicators like serum bilirubin, cholesterol levels, ALT, AST, platelets, INR, and GGT. Hepatic steatosis was assessed using Fasting Lipid Profile, Fibroscan/Shearwave ultrasonography, and Liver Attenuation Index (LAI) from CT scans. Descriptive statistics were applied, and gender-based variations in biochemical markers, CAP, and LSM were analyzed using independent t-tests. Chi-square tests evaluated gender differences in steatosis identified by pathology and CAP. A significance level of P &lt; 0.05 was used. Results: Of the 67 donors, 49 were males, with a mean age of 30.1 ± 8.8 years. Pathology revealed mild steatosis in 35 and moderate steatosis in 5 donors. Ultrasound showed normal liver echotexture in 47 subjects, while 18 had fatty liver. CAP findings indicated mild steatosis in both genders, with females showing higher values (P = 0.02) and more advanced steatosis (P &lt; 0.01). Mean LSM was 4.6 ± 1.53 kPa, indicating normal liver stiffness. LAI findings suggested 37 donors required further evaluation. Among overweight donors, 22% had advanced steatosis compared to 14% in the healthy-weight group. Conclusion: Ultrasound-directed CAP, LSM, and BMI are effective non-invasive tools for diagnosing hepatic steatosis in potential liver donors.

Multiple brain abscesses caused by Nocardia farcinica infection after hand injury: A case report and literature review.

Nocardia infection is commonly regarded as an opportunistic pulmonary pathogen affecting debilitated or immunocompromised individuals. Brain abscesses caused by Nocardia farcinica are rare and pose a diagnostic challenge. Traditional diagnostic techniques for identifying Nocardia species, such as blood culture, microscopy, and pathology, have shown inadequate performance. In the reported case, we applied metagenomic next-generation sequencing (mNGS) to diagnose a case of brain abscess due to N. farcinica. A 66-year-old female developed a brain abscess after sustaining a hand injury. The patient exhibited a gradual change in personality and experienced tremors in her right upper limb for a duration of 1 month. The pathogen responsible for the multiple brain abscesses was identified in the cerebrospinal fluid as N. farcinica through mNGS. Antibiotic treatment included trimethoprim-sulfamethoxazole, linezolid, amikacin, meropenem, and moxifloxacin. The patient's symptoms and signs improved significantly after administration of antibiotics to which the pathogen is known to be sensitive. After 5 months of follow-up, magnetic resonance imaging of the head showed that the abscess was basically cured. The patient lived a normal life with no adverse drug reactions. Nocardia brain infection is characterized by an insidious onset and lacks distinctive clinical and imaging features. mNGS was advantageous for the timely identification and management of Nocardia-associated brain abscess in the present case and obviated the need for invasive brain surgery. Expeditious and precise diagnosis coupled with prompt antibiotic therapy can significantly reduce the mortality rate associated with this condition.