We previously reported that transforming growth factor-beta 1 (TGF-β1) promoted breast cancer progression and metastasis through inhibiting the expression of miR-4638-3p via directly targeting activating transcription factor 3 (ATF3). The present study aimed to elucidate the mechanisms of TGF-β1 downregulating ATF3 targeting miR-4638-3p via circRNA in MDA-MB231 cells.

Three triple-negative human breast cancer cells (MDA-MB231, MDA-MB468, and MDA-MB453) were employed. In-silico analyses were used to identify the list of circRNAs targeting miR-4638-3p. RT-qPCR was performed to determine the expression of shortlisted circRNAs. Transient transfection and western blot analyses were carried out to identify the functional role of circ_DISP3. A dual-luciferase reporter assay was used to identify the direct binding of circ_DISP3 and miR-4638-3p.

There was an inverse correlation between the expression of circ_DISP3 and miR-4638-3p in these cells. Antisense oligos-mediated silencing of circ_DISP3 restored the function of miR-4638-3p, and downregulated ATF3 in MDA-MB231 cells. The luciferase reporter assay identified the direct binding of circ_DISP3 to miR-4638-3p in these cells.

TGF-β1 influences the expression of ATF3 to stimulate circ_DISP3 to sponge miR-4638-3p in hBC cells. Hence, we suggest that the circ_DISP3/miR-4638-3p/ATF3 axis regulated by TGF-β1 may have potential applications for bone-metastatic breast cancer.

Hepatocellular carcinoma (HCC) is an aggressive tumor that usually occurs in patients with chronic liver disease and cirrhosis. Surgical resection is an optimal treatment for HCC, but the 5-year recurrence rates are significantly high. The majority of recurrent HCCs occur through intrahepatic metastasis with local tumor progression, and less than 20% of recurrences are extrahepatic metastases. HCC with gastric metastasis is extremely rare, and it is easily misdiagnosed as primary gastric cancer with liver metastasis. An 80-year-old male chronic hepatitis B virus carrier had received lamivudine and entecavir for years and was regularly followed up in the clinic. He had a 3.5 cm solitary HCC with microvascular invasion and received curative surgical resection in 2009. In 2013, he developed a 1.3 cm solitary HCC again and was treated with combination therapy with radiofrequency ablation and pure ethanol injection. Afterwards, he was followed every 3–6 months and was HCC-free. Three years later, in 2016, endoscopy for intermittent epigastralgia showed a solitary 4 cm intraluminal gastric subepithelial tumor without mucosal ulcers or erosions over the gastric fundus. All imaging studies, including computed tomography, favored the diagnosis of gastrointestinal stromal tumor (GIST), but the pathology of the tumor proved to be HCC. The patient did not receive any systemic anticancer therapy but only wedge resection of the stomach and remained tumor- and HCC-free until his latest clinic visit in 2023. The current case is unique and indicates the possibility of HCC with late solitary gastric metastasis mimicking GIST. Complete gastric tumor resection ensured an extremely good outcome for the patient, which is different from the devastating prognosis of most cases of HCC with gastric metastasis.

Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development.

Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections.

BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis.

BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.

Takotsubo cardiomyopathy can masquerade as an acute coronary syndrome and present clinically with chest pain and dyspnea, electrocardiogram changes of cardiac ischemia and elevation of cardiac enzymes. Such changes are particularly relevant in cases where Takotsubo cardiomyopathy is associated with subarachnoid hemorrhage, and treatment of acute coronary syndrome with antiplatelet drugs is contraindicated. We describe a case of a 68-year-old woman, who developed ventricular changes consistent with Takotsubo cardiomyopathy following an aneurysmal subarachnoid hemorrhage. The patient presented with collapse and vomiting, initial workup revealed anterior ST-elevation electrocardiogram changes, increased troponin I, and a chest radiograph suggestive of acute cardiac failure. In light of this, the patient was managed initially as an acute coronary syndrome with antiplatelet medication. An echocardiogram showed acute left ventricular systolic dysfunction with apical ballooning. After 3 days of hospitalization, she became increasingly drowsy with a worsening headache. Computed tomography of the head revealed intracerebral hemorrhage and bilateral subarachnoid hemorrhage and computed tomography angiography demonstrated a 9 × 5 mm A2 aneurysm. She subsequently underwent embolization to treat the ruptured aneurysm. She recovered well neurologically, and subsequent cardiac imaging revealed a complete resolution of her prior issues.

To standardize the diagnosis, treatment, and management of esophagogastric variceal bleeding (EVB) in patients with cirrhotic portal hypertension, the Chinese Society of Hepatology, the Chinese Society of Gastroenterology, and the Chinese Society of Digestive Endoscopy of the Chinese Medical Association brought together relevant experts, reviewed the latest national and international progress in clinical research on EVB in cirrhotic portal hypertension, and followed evidence-based medicine to update the Guidelines on the Management of EVB in Cirrhotic Portal Hypertension. The guidelines provide recommendations for the diagnosis, treatment, and management of EVB in cirrhotic portal hypertension and with the aim to improve the level of clinical treatment of EVB in patients with cirrhotic portal hypertension.

Bone marrow-derived mesenchymal stem cells (MSCs), possess the unique ability of self-renewal and development into specialized cells, and long-lived cells with specific metabolic needs. It has been demonstrated that autophagy is essential for MSC differentiation, quiescence, activation, and self-renewal. The present study aims to elucidate how autophagy influences bone marrow-derived MSC post-novodrin-prompted liver dysfunction.

Hepatic dysfunction was induced in rats using novodrin (100 mg/kg, subcutaneously), which was divided into two doses for two alternative days, followed by the treatment with 100 µL of intravenous injection of allogeneic MSCs (5 × 106).

A month preceding MSC therapy, a marked decline in liver function biomarkers, including alanine aminotransferase and aspartate aminotransferase, was observed, in addition to the significant decrease in oxidative stress biomarker, lipid peroxide. Meanwhile, novodrin significantly elevated the gene expression of cell survival biomarkers, including signal transducer and activator of transcription, phosphatidylinositol-3-kinase, and serine/threonine kinase-1, in addition to the concomitant increase in oncogenic biomarker, phosphatase and tensin homolog, and this was reversed post-MSC implantation. Furthermore, the autophagy biomarkers, including Beclin-1 and X-box binding protein 1, were restored post-MSC implantation. Moreover, the MSCs labeled with the PKH26 red fluorescent dye were sown into the injured liver tissue, which presented with hepatic tissues with a nearly normal architecture as confirmed through histopathological examination.

The present study demonstrated that autophagy is essential for bone marrow-derived MSC in novodrin-induced liver dysfunction.

Newborns, with their low immune system, lack of self-care ability, and inability to express discomfort through language, face challenges during the treatment of diseases, especially during intravenous infusion treatments where extravasation can occur. The inability of nurses to immediately detect extravasation often leads to severe consequences, including disability and even death. This increases the pain and treatment costs for children and places a heavy burden on healthcare professionals, hospitals, and society. Neonatal infusion extravasation is widespread during intravenous infusion and is influenced by various factors. Therefore, this article aims to review the research progress on relevant influencing factors that cause neonatal infusion extravasation.

Breast cancer can develop either in the tubes connecting the lobules of milk-producing glands to the nipple or the lobules themselves. GLOBOCAN 2021 reported an estimated 14.1 million new instances of cancer, 8.2 million cancer-related deaths, and 32.6 million people who had cancer for at least five years after their diagnosis. The development of genomic instability enables the acquisition of functional cells to become cancerous allowing the survival, proliferation, and dissemination of malignancy. These cells develop distinctive abilities as a result of acquired rare genetic mutations. Multistep tumor growth is caused by a succession of clonal expansions that are set off by the accidental discovery of an enabling mutant genotype. Hence, it is vital to identify defective genes in breast cancer and breast cancer therapy to mitigate the need for treatment. Critical analyses of various defective genes are compiled in this review.

Bacteriocins of probiotic lactic acid bacteria have been used as bio-preservatives to improve food safety and extend the storage period of some food types. This study explored the impact of plantaricin LDL, a bacteriocins purified from the potential probiotic strain, Lactobacillus plantarum LD1, on inhibiting the growth and biofilm formation of food spoilage bacteria in milk.

The antimicrobial and anti-biofilm activity of Plantaricin LD1 was determined against a food-borne pathogen, Staphylococcus aureus subsp. aureus ATCC 25923. The efficacy of plantaricin LD1 against S. aureus subsp. aureus ATCC 25923 was also tested in the milk.

Plantaricin LD1 had a minimum inhibitory concentration of 79.16 µg/mL and minimum bactericidal concentration of 158.33 µg/mL against S. aureus subsp. aureus ATCC 25923. Biofilm formation of S. aureus subsp. aureus ATCC 25923 was completely inhibited in the presence of 79.16 µg/mL of plantaricin LD1. Complete loss of cell viability in milk was observed after treatment with double minimum inhibitory concentration (158.33 µg/mL) of plantaricin LD1 at 48 hrs.

Our findings illustrate the antimicrobial and anti-biofilm activity of plantaricin LD1 against S. aureus subsp. aureus ATCC 25923 in milk. These results suggest that plantaricin LD1 can be used as a natural preservative to expand the shelf-life of milk.

Interleukin 27 (IL-27) is a cytokine consisting of two subunits, p28 and EBI3, and is a key mediator in regulating the differentiation of TCD4 + cells while playing a crucial role in immune-related disorders. This study aims to elucidate the possible association between IL-27p28 single nucleotide polymorphisms (SNPs), IL-27 serum levels, and the risk of allergic rhinitis (AR).

Blood samples were collected from 130 patients with AR and 130 healthy individuals, and DNA and serum were separated. The relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR was evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. The serum levels of IL-27 in the participants were determined using enzyme-linked immunosorbent assay.

Our results did not show a significant relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR or serum IL-27 levels. However, our results showed a significant decrease in the serum level of IL-27 in patients with AR (342 ± 299 pg/mL) compared to healthy subjects (455 ± 274 pg/mL) (p = 0.02).

Our results suggest that IL-27p28 SNPs (rs181206 and rs153109) are not associated with susceptibility to AR, but that decreased serum IL-27 levels may be associated with the development of AR.

The gut microbiome has been well-established in its role of regulating the onset of many gastrointestinal disorders. Recent evidence has shown a bidirectional relationship between the intestinal microbiota and the liver. The gut microbiome may affect liver disease progression through its bacterial composition, the metabolism of bile acids, and the translocation of bacterial products. Modulation of dysbiosis may be considered as a potential therapeutic target for liver disease regardless of the underlying cause. Continuing to identify parts of the gut-liver axis that are disordered in different etiologies of liver disease may offer insight into potential interventions to restore homeostasis. Thus, this review will focus on exploring some of the major gut microbiome targeted therapies for liver disease, including probiotics, prebiotics, and fecal microbiota transplantation.

Over the past decade, the approach to gastrointestinal (GI) neuroendocrine tumors (NETs) has increasingly included endoscopic resection (ER) techniques. Underwater endoscopic mucosal resection (UEMR) has been introduced as a potential alternative to conventional mucosectomy. The objective of this systematic review is to investigate the feasibility and outcomes of UEMR in the treatment of GI NETs and to provide a reference for clinical management options.

A systematic search of PubMed, Cochrane Library, and EMBASE was performed to identify guidelines and primary literature published up to 8 August 2023.

Our review did not find any UEMR results for esophageal NETs. For gastric NETs, there is only one case series pilot study with two patients with G1 tumors, that were completely resected without complications. For duodenal NETs eligible for ER, a total of 11 cases are reported, with success in all procedures. For ileum NETs, there is only one report, for an outlier case. Finally, UEMR is best indicated for rectal tumors, where it is an alternative to endoscopic mucosal resection or endoscopic submucosal dissection techniques, as shown in four comparative studies.

UEMR is presented as a good option for selected cases, as it has notable advantages in that it can achieve a complete histological resection at a lower cost, with a short procedure time, and does not require advanced endoscopic skills to ensure good results.

In this systematic review, we evaluated the efficacy, mechanisms and safety of three neuromodulation therapies in patients with gastroesophageal reflux disease (GERD), including the effect of neuromodulation therapies on symptoms and key GERD pathophysiologies, lower esophageal sphincter (LES) pressure, esophageal motility, gastric motility, and parasympathetic activity. The first therapy is LES electrical stimulation using an implantable electrical stimulator, the second is transcutaneous electrical acustimulation, and the third is manual acupuncture.

A systematic review of literature according to the PRISMA guidelines was performed. Online databases searched include Medline (Ovid), Embase, and PubMed. Studies were assessed for inclusion and exclusion criteria with Covidence, a systematic review software.

The analysis included thirteen clinical studies. Four papers included were registered under two open-label trials on ClinicalTrials.gov for LES electrical stimulation; Five randomized trials with sham-treated controls were analyzed for transcutaneous electrical acustimulation; Four studies, including three involving standard therapy controls and one involving sham-treated controls were included for manual acupuncture. All evaluated studies demonstrated significant beneficial effects on GERD symptoms, using patient-completed questionnaires, objective 24-h measurement of esophageal pH, and patient-reported use of proton pump inhibitors. In evaluating the effect on key GERD pathophysiologies, electrical stimulation significantly increased LES pressure, and transcutaneous electrical acustimulation significantly improved esophageal motility, gastric motility, and parasympathetic activity. None of the evaluated neuromodulation methods produced severe adverse effects.

Cumulative evidence from the evaluated studies indicates that neuromodulation therapies were effective in treating the GERD symptoms and key underlying GERD pathophysiologies. They are thus valuable options for individualized GERD treatment.

Many (+)RNA viruses employ translational recoding mechanisms, such as programmed ribosomal readthrough and ribosomal frameshifting, to direct a fraction of translating ribosomes in the infected cell to recode or bypass a stop codon in the zero reading frame and continue translation, thus producing protein isoforms with distinct functions. This creates a means to regulate both the quantity and time of synthesis of canonical and fusion proteins. The viral programmed ribosomal readthrough and ribosomal frameshifting signals are variable, with some being just short RNA sequences encompassing a stop codon, whereas others require elaborate RNA-RNA and RNA-protein interactions. Within virus evolutionary lineages, a given type of recoding signal is not universal, and its presence may be specific to a virus family, species, or even strain. It is possible that the establishment of virus recoding mechanisms and expression patterns occurs after the appearance of extant virus lineages, and these recoding signals might be acquired on multiple occasions during evolution. Recoding signals are the key regulators of gene expression in several clinically important viruses, such as human immunodeficiency viruses 1 and 2, human T-cell lymphotropic retroviruses, and severe acute respiratory syndrome coronavirus 2, as well as in a number of other animal and plant viruses of concern. The knowledge of viral recoding mechanisms is expected to provide new perspectives for the development of antiviral and synthetic biology strategies.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Nanoparticle (NP) drug delivery systems have been developed recently to resolve the obstacle of drug resistance, contributing to the effective drug delivery to the target organ. A comparative study was carried out herein between doxorubicin (DOX), doxorubicin-loaded titanium NPs, DOX-loaded lactoferrin NPs, DOX-NPs, and PEGylated-doxorubicin (PEG-DOX) on the reno-carcinogenic impact of 3-methylcholanthrene (CA).

In-vivo models were exposed to CA at a dose of 50 mg/kg body weight and left for 3 months till the incidence of chronic kidney disease, followed by one month of treatment with the aforementioned nanomedicines.

CA downregulated DOX resistance biomarkers, including the gene expression of KRAS, FKBP5, P53, and JAK2, and the kidney tumor marker arginase II. In addition, CA increased the levels of the kidney biomarkers creatinine and urea as well as the minerals chloride and magnesium. Decreased gene expression of FKBP5, KRAS, P53, and JAK2 was reversed after the treatment with DOX-loaded titanium NPs, DOX-NPs, DOX-loaded lactoferrin NPs, and PEG-DOX. PEG-DOX abolished the detrimental effects of CA via upregulating the gene expression of the immunophilin protein (FKBP5), the oncogene (KRAS), the tumor suppressor gene (P53), and JAK2, which indicate DOX drug resistance via regulating cell differentiation, division and apoptosis.

PEG-DOX restored renal function and resolved DOX resistance via KRAS, FKBP5, P53, and JAK2 signaling pathways manipulation; consequently, PEG-DOX may provide a useful adjunct treatment for chronic kidney disease.

Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy that presents with dismal outcomes and a high metastatic propensity. The prognostic factors as well as therapeutic regimens remain largely unknown due to the rarity of SNMM. This study aimed to assess the characteristics of SNMM patients associated with a better prognosis.

We performed an observational cross-sectional study to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and anti-programmed death-ligand 1 (PD-L1) therapy in 12 SNNM patients who were diagnosed at our institution and treated with anti-PD-L1 from 2011 to 2021.

Of the 12 cases, five (41.7%) displayed brisk TIL activity, while seven (58.3%) had non-brisk TIL activity. The BRAF V600E mutation was not identified in any of the 12 cases by mutational analysis. The expression of PD-L1 was identified in 5 out of 10 SNMM cases (50%). Brisk TILs might be associated with a better prognosis compared with non-brisk TILs (p = 0.036).

Brisk TILs might serve as a potential prognostic factor in SNMM patients. Anti-PD-L1 therapy may be used as a potential therapeutic strategy for treating SNMM.

Hepatic diseases have constituted a significant global problem for over two decades, numerous factors contribute to these diseases, and most eventually result in hepatocellular carcinoma. A particular pivotal factor responsible for hepatic diseases is the abnormal functioning of various metabolic processes. Pyruvate kinase is a crucial regulator of the glycolytic pathway, and overexpression of pyruvate kinase isoform M2 (PKM2) has been observed with various hepatic abnormalities due to genetic malfunctioning and other contributing factors. The present scenario for diagnosing and treating hepatic diseases includes surgery and immunosuppressant therapies. Kinase modulation may also be a potential therapeutic measure for rectifying hepatic diseases, and this can serve as a potential approach. This review summarizes the malfunctions and significance of PKM2 regulation and explores the potential of PKM2 as a target for treating hepatic abnormalities.

Understanding the characteristics of cancer cells is critical for developing enhanced therapies and diagnoses. The super-enhancer notion has been given from the angle of gene regulation in order to properly appreciate the molecular mechanisms behind the identities of distinct cell types. A variety of distinguishing features of super-enhancers have contributed to the findings which link gene regulation and biomolecular condensates. This is typically mediated via liquid-liquid phase separation. Several lines of evidence have pointed to alterations in molecular and biophysical principles in cancer cells, notably those linked to gene regulation and cell signaling. All these findings hint to biomolecular condensate change as a major mechanism by which cancer cells acquire distinct cancer characteristic traits and offer functional innovation for cancer initiation and progression. Liquid-liquid phase separation has recently been used for sorting all the processes taking place in the cell for the formation of biomolecular condensates (membrane-free organelles). Recent studies on biomolecular condensates have found that their production and regulation are associated with cancer. Here, we review the evidence that production and degradation of biomolecular condensates are linked to cancer development and progression. As they are linked to cancers, they can be used in cancer research and to devise new cancer therapies, for example, condensate perturbation.