Diagnosing and treating cytopenic myelofibrosis in children is challenging due to the wide spectrum of clinical and pathological features, underlying etiologies, and variable therapeutic responses. In this review, we summarize the related literature and present our diagnostic algorithm to differentiate pediatric myelofibrosis and guide therapy. In brief, primary myelofibrosis is extremely rare in children, while myelofibrosis secondary to non-neoplastic or neoplastic disorders should be thoroughly ruled out in ambiguous cases. Moreover, it is reasonable to closely follow up patients and repeat bone marrow biopsy before reaching a definitive diagnosis.

Oxidative stress could be a key process in acyclovir (ACV)-induced nephrotoxicity. N-acetylcysteine (NAC) is a water-soluble antioxidant with anti-inflammatory activity. This study aimed to evaluate the protective effect of NAC on ACV-induced nephrotoxicity in adult Wistar rats.

Forty adult male Wistar rats (200–220 g) were used. The rats were randomly divided into eight groups (n = 5/group) and were treated intraperitoneally daily for seven days as follows: Group 1 (Control) was administered water (0.2mL), while groups 2–4 were administered NAC (25, 50, and 100 mg/kg). Group 5 was administered ACV (150 mg/kg), while groups 6–8 were supplemented with NAC (25, 50, and 100 mg/kg) prior to treatment with ACV (150 mg/kg). On day 8, the rats were weighed and euthanized, and blood samples were collected for the assessment of biochemical markers. The kidneys were weighed and subjected to oxidative stress markers and histological evaluations.

ACV had no significant (p > 0.05) effects on the body and kidney weights of rats compared to the control. ACV produced significant (p < 0.001) elevations in kidney malondialdehyde, serum urea, creatinine, and uric acid levels in rats, which differed from the control. There were significant (p < 0.001) decreases in kidney glutathione, superoxide dismutase, peroxidase, and catalase, as well as serum chloride, potassium, bicarbonate, and sodium levels in ACV-treated rats compared to the control. ACV caused widening of Bowman’s space and tubular necrosis in the kidneys of rats. Nonetheless, NAC supplementation abrogated ACV-induced nephrotoxicity in a dose-dependent manner. Kidney histology was restored by NAC supplementation.

NAC protected against ACV-induced nephrotoxicity. This finding shows that NAC may have therapeutic potential for nephrotoxicity caused by ACV.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition affecting the ileum, colon, and rectum, including ulcerative colitis and Crohn’s disease. Clinical symptoms include abdominal pain, diarrhea, and even bloody stools. The intestinal barrier is the first line of defense between the intestinal tract and the external environment, and maintaining its stability is essential for intestinal health. On one hand, it enables the digestion and absorption of water and nutrients; on the other, it plays a crucial role in reducing the absorption of toxins and the invasion of pathogens. Damage to the intestinal barrier has become one of the most important factors in the onset and progression of IBD. However, there is currently no literature that systematically reviews the mechanisms of the intestinal barrier in the pathogenesis of IBD and the factors influencing it. In this paper, we aimed to systematically elaborate on the role of the intestinal barrier in IBD through the perspectives of oxidative stress, intestinal flora, and cellular autophagy. Our goal was to explore the mechanisms of the intestinal barrier in IBD more deeply and to provide new insights for the diagnosis and treatment of IBD. This article will summarize the composition of the intestinal barrier, the factors affecting it, and strategies to protect it.

Patients with acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) are at high risk of bleeding with traditional artificial liver support systems. To address the bleeding risk in liver failure patients, the safety of regional mesylate anticoagulation (RMA) in centrifugation artificial liver support systems (cALSS) is proposed for study.

In this prospective single-arm study, ALF and ACLF patients were treated with cALSS using RMA. Coagulation function was monitored, and the predictors of mesylate dose were analyzed using the area under the curve (AUC). Blood ammonia, model for end-stage liver disease scores, and survival rates at 28 and 90 days were assessed.

All 57 patients showed no new bleeding within 24 h post-cALSS. Most disseminated intravascular coagulation indicators improved at 0.5 h and 24 h post-cALSS. Thromboelastography showed hypocoagulability at 0.5 h post-cALSS. Univariate and multivariate analyses identified pre-R and pre-MA as key factors for R exceeding 10 m at 0.5 h post-cALSS, with odds ratios of 0.91 (95% confidence interval (CI): 0.84–0.98) and 2.03 (95% CI: 1.05–3.90), respectively, P < 0.05. The predictive values were pre-MA ≤ 38 mm (AUC = 0.817, 95% CI [0.690–0.907], P < 0.001) and pre-R > 6.3 m (AUC = 0.790, 95% CI [0.661–0.888], P < 0.001). Patients showed improvements in blood ammonia and model for end-stage liver disease scores after the last session, especially those with high initial levels (>80 µmol/L and >30). The 28-day and 90-day survival rates of ALF patients were similar to those of ACLF patients.

cALSS with RMA is safe for liver failure patients with a high risk of bleeding. Adjusting the mesylate dose based on pre-R and pre-MA enhances safety.

Breast cancer is one of the leading causes of mortality among women worldwide. Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown. This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs. Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs. Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins. A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction. Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Ablation of TNIP1 induced growth arrest in breast cancer cells. TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1. CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells. Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

TNIP1 regulates the proliferation and apoptosis of breast cancer cells, suggesting that TNIP1 may serve as a potential biomarker for breast cancer.

Experimental models using 2/3 partial hepatectomy or chemical injury have helped identify the pathways associated with liver regeneration (LR). Several microRNAs (miRNAs) have been identified as modulators of LR, but the molecular mechanisms underlying their activity are still unclear. Given the development of new therapies targeting miRNAs, this is an important question to address. This review discusses recent studies exploring the molecular mechanisms of miRNA-dependent regulation of LR. In particular, the finding that circ-RBM23 promotes LR by sequestering cytoplasmic miRNA139-5p has furthered the understanding of the molecular mechanisms underlying circRNA activity. Interestingly, although miRNAs are generally considered negative regulators of their target mRNAs, miRNAs182-5p promotes LR by upregulating Cyp7a. Furthermore, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) were shown to enhance LR after 2/3 partial hepatectomy by releasing miRNAs that inhibit gene expression to promote an anti-inflammatory response or miRNA-regulatory factors. Since the administration of MSCs-EVs has no hepatotoxic side effects, this may represent a therapeutic strategy to promote LR. miRNAs also mediate LR after chemical injury. This is the case for miR194 and miR21, whose downregulation activates pro-regeneration pathways to ameliorate acetaminophen-induced liver injury. In addition, the downregulation of miR21 has been shown to improve autophagy and haemostasis after acetaminophen overdose. Although further studies are needed to improve their efficacy as therapeutics, the evidence gathered in this review has led to a better understanding of the molecular mechanisms associated with the control of LR by miRNAs.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been escalating annually, positioning it as the leading cause of chronic liver disease worldwide. Ursolic acid has demonstrated promising therapeutic efficacy in managing MASLD, thereby justifying the need for an in-depth exploration of its pharmacological mechanisms. This study aimed to investigate elucidate the therapeutic mechanisms by which ursolic acid modulates estrogen conversion in the treatment of MASLD.

Building upon prior studies that have highlighted the potent anti-inflammatory effects of ursolic acid and its specific targeting of 17β-hydroxysteroid dehydrogenase 14 (HSD17B14), this investigation employed a western diet to induce MASLD in murine models with varying severities over different time intervals.

The protein expression of HSD17B14 initially increased, followed by a subsequent decrease. This trend was accompanied by corresponding changes in 17β-estradiol (E2) and estrone (E1) levels. Intervention with ursolic acid resulted in a reduction in HSD17B14 and E1 levels during the phase of high HSD17B14 expression, while simultaneously elevating E2 levels. In steatotic hepatocytes, E1 promoted cellular inflammation, whereas E2 exhibited anti-inflammatory effects. However, the alleviated effects of E2 were antagonized by HSD17B14. As expected, ursolic acid modulated HSD17B14, thereby mitigating the inflammatory response in steatotic hepatocytes.

HSD17B14, a crucial enzyme regulating the balance between E1 and E2, catalyzes the conversion of estrogen E2 into E1, thereby exacerbating tissue inflammation induced by metabolic stress. Ursolic acid, by modulating HSD17B14-mediated estrogen conversion, appears to ameliorate immune-related inflammation in MASLD.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.