Peroxisome proliferator-activated receptors (PPARs) are a superfamily of nuclear transcription receptors, consisting of PPARα, PPARγ, and PPARβ/δ, which are highly expressed in the liver. They control and modulate the expression of a large number of genes involved in metabolism and energy homeostasis, oxidative stress, inflammation, and even apoptosis in the liver. Therefore, they have critical roles in the pathophysiology of hepatic diseases. This review provides a general insight into the role of PPARs in liver diseases and some of their agonists in the clinic.

Achieving and maintaining quality is of utmost importance in laboratory operations for the best possible patient care. The concepts of quality control and related quality procedures and programs are relatively new and less well understood in histopathology laboratories than in other sections of clinical laboratories, particularly in developing countries. This is because the main product from these laboratories consists of descriptive, opinion-based reports rather than numerical reports as in other fields of laboratory medicine, and most of the work is still manual and involves multiple steps. The scope and extent of quality schemes in histopathology laboratories are very broad and complex, requiring coordinated and concerted efforts on the part of all stakeholders to achieve and maintain quality services in these laboratories. There is a need to create awareness among the pathologist community and other healthcare members about the necessity of quality assurance and improvement schemes in these laboratories to achieve optimal patient care. This paper reviewed the scope and extent of quality schemes in histopathology laboratories.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.

Melanoma has become a severe burden for human beings, with high mortality and a growing incidence. Currently, various nanomedicines integrated with novel therapeutic strategies and precision delivery have been developed to treat melanoma. Although great achievements have been made in the development of nanomedicines, clinical translation is lagging far behind. In this review, three research questions are raised to elucidate the bibliometric study on nanomedicines as melanoma therapeutics. The basic bibliometric properties are presented and analyzed. International cooperation and research foci are emphasized. Finally, future research directions for nanomedicines to promote clinical translation are raised, and several feasible suggestions are proposed. We believe that this review could serve as a guideline document for the development of nanomedicines for melanoma therapeutics.

As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear.

We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities. We also employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate the roles of ADAR1 in sepsis-induced liver injury. Finally, we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in sepsis.

PBMCs from patients with sepsis had obvious apoptotic morphological features. Single-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes, with significantly elevated ADAR1 and BCL2A1 expression in severe sepsis. CLP-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 overexpression. ADAR1 directly bound to pre-miR-122 to modulate miR-122 biosynthesis. miR-122 was an upstream regulator of BCL2A1. Furthermore, ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver injury.

The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling pathway. The study provides novel insights into the development of therapeutic interventions in sepsis.

Liver fibrosis is a reversible condition that occurs in the early stages of chronic liver disease. To develop effective treatments for liver fibrosis, understanding the underlying mechanism is crucial. The NOD-like receptor protein 3 (NLRP3) inflammasome, which is a part of the innate immune system, plays a crucial role in the progression of various inflammatory diseases. NLRP3 activation is also important in the development of various liver diseases, including viral hepatitis, alcoholic or nonalcoholic liver disease, and autoimmune liver disease. This review discusses the role of NLRP3 and its associated molecules in the development of liver fibrosis. It also highlights the signal pathways involved in NLRP3 activation, their downstream effects on liver disease progression, and potential therapeutic targets in liver fibrosis. Further research is encouraged to develop effective treatments for liver fibrosis.

As a subunit of the condensin complex, NCAPG has an important role in maintaining chromosome condensation, but its biological function and regulatory mechanism in hepatocellular carcinoma (HCC) remains undefined.

The prognostic ability of NCAPG in HCC patients was examined by univariate and multivariate Cox regression analysis. ROC curves were plotted to compare the predictive ability of NCAPG and AFP. Double luciferase reporter system, and ChIP were used to investigate transcriptional potential of E2F1 to NCAPG. Pyroptosis was observed by scanning electron microscopy. Protein expression of NCAPG, E2F1, and major proteins constituting NLRP3 inflammasome was determined by western blotting and ELISA. An in vivo tumor formation assay was conducted to verify the in vitro results.

Up-regulated NCAPG was identified in HCC tissues compared with adjacent tissue and high NCAPG was positively correlated with poor prognosis. Serum NCAPG mRNA level was a prognostic factor in HCC patients and also a diagnostic factor with higher predictive ability compared with AFP [AUROC 0.766 (95% CI: 0.650–0.881) vs. 0.649 (95% CI 0.506–0.793)]. HBx transfection resulted in concomitant up-regulation of E2F1 and NCAPG. E2F1 significantly increased the activity of luciferase reporter fused with NCAPG reporter, and the interaction of E2F1 and NCAPG gene was confirmed by ChIP. Silencing of E2F1 resulted in significant down-regulation of NCAPG. Knockdown of NCAPG promote pyroptosis mediated by NLRP3 inflammasome activation in multiple HCC cell lines and also suppressed tumorigenesis in vitro.

We identified a novel role of NCAPG in the regulation of NLRP3 inflammasome-mediated pyroptosis, which was regulated by its upstream transactivator, E2F1. The role of E2F1-NCAPG-NLRP3 regulation of pyroptosis network may be a potential target in HCC treatment.

No previous study has been conducted in Nigeria on the role of neutrophil elastase in predicting preterm birth. The present study aimed to determine the role of the neutrophil elastase test in predicting birth in women with preterm labor.

The present prospective cohort study recruited 83 pregnant women with preterm labor between 28 and 36+6 weeks of gestation, and followed up these subjects for 14 days. The controls comprised 85 pregnant women without preterm labor. The cervicovaginal fluid was collected and tested using the neutrophil elastase test. Then, the sensitivity, specificity, and positive and negative predictive parameters were determined. Afterward, the data were scrutinized using the SPSS arithmetic software (Sort23).

Among the 168 pregnant women analyzed in the present study, 83 pregnant women were assigned to the preterm labor group, and 85 pregnant women were assigned to the control group. Furthermore, among the 83 pregnant women in the preterm labor group, 11 women had spontaneous preterm delivery, leading to a spontaneous preterm birth proportion of 13.3%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the neutrophil elastase test within 14 days post-enrollment were 93.8%, 61.2%, 36.6%, 97.6%, and 67.5%, respectively, for the general population, and 87.5%, 66.7%, 35.0%, 96.3%, and 70.2%, respectively, for subjects at <35 weeks of gestation. The positive and negative likelihood ratios for preterm birth prediction were 2.62 and 0.19, respectively.

The neutrophil elastase test exhibited high predictive accuracy in pregnant women with preterm labor, when compared to the controls, based on the sensitivity and negative predictive value, but this had poor positive predictive values. The neutrophil elastase test may be used as a screening test, but not as a potential predictive test, in the routine clinical setting.

Hypoxia-inducible factor-1 alpha (HIF-1α) is usually regarded as a core regulator of hypoxic response. Persistent inflammation and impaired wound healing are common manifestations of diabetic foot ulcer (DFU). In normal wounds, HIF-1α and its related regulatory molecules, such as vascular endothelial growth factor and inducible nitric oxide synthase, are activated by hypoxia signals, which in turn promote wound healing. However, abnormal regulation of the HIF-1α signaling pathway by hyperglycemia leads to impaired wound healing in DFU. In this review, we highlight the tissue-specific and stage-specific effects of the HIF-1α signaling pathway in DFU. In the early stage of DFU, HIF-1α in inflammatory cells is over-upregulated by hyperglycemia, causing the activation of nuclear factor-κB and the inducible nitric oxide synthase-mediated pro-inflammatory signaling pathway, leading to sustained inflammation, which is deleterious. In the late stage of DFU, HIF-1α in endothelial cells and keratinocytes is inhibited by hyperglycemia, which leads to the downregulation of vascular endothelial growth factor expression, resulting in insufficient angiogenesis and difficult healing at the wound site. In this review, we discuss recent advances in the knowledge of the HIF-1α signaling pathway and the key targeted molecules in impaired wound healing of DFU. We also summarize the drugs currently in clinical trials that target HIF-1α or its downstream molecules, recapitulate current gaps in our knowledge, and propose rational therapeutic strategies for DFU based on the action characteristics of HIF-1α.

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.