Esophagogastroduodenoscopy and colonoscopy play important roles in diagnosing gastrointestinal bleeding; however, they may sometimes fail to identify the source of the bleeding during the initial examination. In such cases, repeated endoscopic examination may be beneficial. Currently, no consensus exists on which patients would benefit from repeated examination. In this review, we discuss the role of repeated endoscopy and conclude that repeated esophagogastroduodenoscopy and colonoscopy can help improve detection rates. It is particularly valuable to repeat the procedure when the quality of the initial endoscopy is poor, the patient’s condition deteriorates, or other examinations suggest that lesions are within the scope of endoscopy.

Peroxisome proliferator-activated receptors (PPARs) participate in the fatty acid oxidation, the homeostasis of lipid and glucose metabolism, the regulation of insulin sensitivity, and numerous metabolic processes, making them novel and important therapeutic targets for cancer treatment. However, PPARs manifest dual functions, wherein their activation and inhibition engender diverse outcomes in different types of tumors. The specificity of drugs for tumors is also a challenge when targeting PPARs. In recent years, proteolysis targeting chimeras (PROTACs) have gained significant attention in the field of cancer therapy, demonstrating potent therapeutic potential in both basic and clinical research. Furthermore, heterobifunctional molecules derived from PROTACs have ventured into domains that extend beyond protein degradation. Currently, there are no developed PPAR-targeting PROTACs. Therefore, our review delves into various aspects, including the dual roles of PPARs, known inhibitors, agonists, ligands, and co-crystal structures, and explores the feasibility and advantages of PPAR-targeting PROTACs and other heterobifunctional molecules in cancer therapy.

Breast cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection of breast cancer significantly improves outcomes and survival rates, minimizing treatments. Imaging techniques are critical in identifying abnormalities and diagnosing breast cancer at its earliest stages, often before clinical symptoms emerge. Mammography remains standard for screening in average-risk women, while supplementary methods like ultrasound, magnetic resonance imaging, and tomosynthesis enhance detection rates, particularly in women with dense breasts or those at high risk. Given that certain factors, such as family history, age, genetic mutations, and breast density, affect the risk of developing breast cancer, some women may benefit from earlier or more frequent screenings. Personalized screening protocols are becoming more common, tailoring the type and frequency of imaging to the individual’s risk profile. Newer technologies, such as molecular breast imaging and contrast-enhanced mammography show promise but require further validation for widespread use. In conclusion, imaging techniques including mammography, ultrasound, magnetic resonance imaging, and newer technologies like three-dimensional mammography and molecular breast imaging are essential tools in the early detection of breast cancer, leading to better outcomes for patients. This literature review provides an overview of current breast cancer imaging methods, their role in early diagnosis, and their effectiveness and limitations.

Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is insufficient to meet the existing demand for this valuable molecule. Therefore, biotechnological approaches are necessary to enhance the isofraxidin content.

Endophytes were isolated from the roots, stems, and leaves of Sarcandra glabra and fermented with Sarcandra glabra, respectively. The target strains capable of increasing isofraxidin content were screened using high-performance liquid chromatography. Their genes were amplified, and the polymerase chain reaction products were sequenced. BLAST analysis was used to compare the sequences with those in GenBank, and a phylogenetic tree was constructed for species identification.

Fifteen endophytic bacteria and six endophytic fungi were isolated from the roots, stems, and leaves of Sarcandra glabra. Among them, Enterobacter, Bacillus wiedmannii, Trametes versicolor from the roots, and Diaporthe celeris and Diaporthe hongkongensis from the leaves increased the isofraxidin content in Sarcandra glabra. The isofraxidin content in Sarcandra glabra fermented by endophytes Enterobacter, Bacillus wiedmannii, Trametes versicolor, Diaporthe celeris, and Diaporthe hongkongensis was 1.37, 1.27, 1.11, 1.40, and 1.16 times higher than in the blank samples, respectively.

The fermentation of Sarcandra glabra with specific endophytes can increase its isofraxidin content. These findings provide preliminary scientific evidence for the potential of using microorganisms to enhance the quality of traditional Chinese medicine.

Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal tracts. However, its presence in body fluids after racing is prohibited by animal racing authorities. The current study aimed to conduct a pilot pharmacokinetic study of BSA in healthy camels. The goal was to obtain initial pharmacokinetic parameters and use these parameters to predict plasma concentrations from the dose and clearance. This will help advise on a withdrawal time for BSA administration before camel racing. The pharmacokinetics of BSA were evaluated in three healthy camels after a single intravenous dose of 0.2 mg/kg body weight. Sensitive liquid chromatography with tandem mass spectrometry was used for the quantification of BSA and the internal standard, ipratropium, in plasma. BSA concentration versus time data were best described by a two-compartment open model. The pharmacokinetic parameters (median and range) were as follows: terminal elimination half-life was 2.29 (1.48–2.46) h, plasma clearance was 1,018.5 (772.4–1,024.0) mL/h/kg, volume of distribution at steady state was 931.9 (700.0–1,068.7) mL/kg, Cmax was 443.9 (351.1–443.9) ng/mL, and Tmax was 0.5 (0.25–0.75) h. BSA’s irrelevant plasma concentration was estimated to be 20 ng/mL. Consequently, it can be concluded that plasma would not contain BSA at the screening level of 20 ng/mL at the usual dose of 0.2 mg/kg body weight 24 h before camel racing.

Metabolic dysfunction-associated steatotic liver disease has emerged as a leading cause of chronic liver disease and cirrhosis in the Western world. With rising rates of obesity, the prevalence of metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis is expected to increase. MASH is associated with chronic hepatic inflammation and progressive liver fibrosis, and significant research is focused on developing pharmacological therapies to reverse these downstream complications. Recent trials have explored various therapeutic targets across metabolic, inflammatory, and fibrogenic pathways aimed at decreasing liver triglycerides, inflammation, lipotoxicity, and fibrosis. Some of these drugs show promise in reversing biomarkers and/or histologic markers of steatohepatitis and fibrosis, although most have been primarily studied in non-cirrhotic patients. However, in the context of the significant unmet medical need of patients with MASH-associated cirrhosis, growing interest in targeting compensated cirrhosis has prompted renewed investment in numerous early clinical and late-stage programs evaluating novel investigational agents in this population. This review summarizes current therapies under evaluation in phase 2 and 3 clinical trials for MASH-related cirrhosis, highlighting drug mechanisms, outcomes, and future research directions.

The tumor microenvironment is a dynamic cellular landscape critical to cancer progression. Within it, tumor-infiltrating lymphocytes hold a dual role, contributing to both tumor suppression and progression. This review synthesized current knowledge on tumor-infiltrating lymphocytes, emphasizing their prognostic significance and therapeutic potential. By dissecting their interactions within the tumor microenvironment and with cancer cells, we sought to uncover the complexities of the immune response in cancer and explored the future direction of immunotherapeutic strategies.

The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism in vitro, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.

MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. Lipidomic analyses were conducted to assess how SOX9 influences hepatic lipid metabolism. RNA sequencing was employed to identify pathways modulated by SOX9 during MASH progression. To elucidate the mechanism further, HepG2 cells were treated with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor to test whether SOX9 acts via AMPK activation.

SOX9 expression was significantly elevated in hepatocytes of MASH mice. Hepatocyte-specific SOX9 deletion exacerbated MCD-induced MASH, whereas overexpression of SOX9 mitigated high-fat, high-fructose-induced MASH. Lipidomic and RNA sequencing analyses revealed that SOX9 suppresses the expression of genes associated with lipid metabolism, inflammation, and fibrosis in MCD-fed mice. Furthermore, SOX9 deletion inhibited AMPK pathway activation, while SOX9 overexpression enhanced it. Notably, administration of an AMPK inhibitor negated the protective effects of SOX9 overexpression, leading to increased lipid accumulation in HepG2 cells.

Our findings demonstrate that SOX9 overexpression alleviates hepatic lipid accumulation in MASH by activating the AMPK pathway. These results highlight SOX9 as a promising therapeutic target for treating MASH.

Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung development, has gained attention for its role in pulmonary fibrosis. While Notch1 and Notch3 have been extensively studied, the involvement of other Notch receptors, especially Notch4, remains less explored. This study aimed to evaluate the impact of Notch4 on lung fibroblast activation and its potential interaction with the transforming growth factor-beta 1 (TGFβ1) signaling.

Primary human lung fibroblasts were transduced with lentivirus containing the intracellular domain of NOTCH4 (N4ICD). Changes in gene expression in transduced cells were assessed using real-time polymerase chain reaction, immunofluorescence staining, and Western blotting. Transcriptomic analysis was also performed on N4ICD-transduced lung fibroblasts.

N4ICD overexpression significantly upregulated key fibrotic markers such as ACTA2 and COL1A1. It also induced the TGFβ1 pathway, as evidenced by SMAD2 phosphorylation and elevated TGFβ1 mRNA level. Transcriptomic analysis revealed that N4ICD-induced cells exhibited characteristics of highly invasive myofibroblasts.

This study establishes Notch4 as a novel contributor to pulmonary fibrosis, by demonstrating its ability to induce myofibroblast differentiation and interact with the TGFβ1 pathway.