Treatment for Gorham-Stout syndrome with a combination of teriparatide and denosumab.

Gorham-Stout syndrome is an aggressive, non-hereditary, and rare disease affecting bone metabolism. Its etiology and pathogenesis remain elusive. The syndrome manifests with diverse clinical symptoms, often leading to frequent misdiagnoses and presenting challenges in treatment. In this study, we report a case of cranial and maxillary osteolysis in a 47-year-old female patient with somatic mutations in the VEGF-A, VEGF-B, and VEGF-C genes and the EPHB4 gene. After treatment with bisphosphonates, this patient still had persistent resorption of the mandible, but switching to a teriparatide and denosumab combination yielded substantial improvement. This study is the first report to show that teriparatide combined with denosumab can be used to treat Gorham-Stout syndrome.

Complete remission of pulmonary alveolar proteinosis after anti-tuberculous chemotherapy: a case report.

Pulmonary alveolar proteinosis (PAP) is a rare respiratory system disorder. Patients with PAP are at risk for a wide variety of secondary infections. This current case report describes a patient with PAP complicated by tuberculosis. A 48-year-old male patient with multiple follow-up chest computed tomography scans that showed predominant diffuse ground glass opacity in both lung fields, presented a few years later with new calcified lesions and pleural effusion. At this point, the associated auxiliary examination indicated the possibility of PAP combined with tuberculosis infection. The patient achieved complete remission after anti-tuberculosis treatment. PAP is an easily overlooked clinical syndrome due to its low prevalence and lack of specific clinical manifestations, especially when combined with other pulmonary lesions. Therefore, clinicians should consider this rare disease in patients presenting with pulmonary disease and plan for its co-morbidity with other secondary outcomes, such as opportunistic infections, which are a common and life-threatening complication in patients with PAP. This case indicates the possibility that anti-tuberculosis therapy can improve alveolar proteinosis in patients with PAP and secondary Mycobacterium tuberculosis infection.

LncPRYP4-3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by targeting RPS4Y2.

Longitudinal studies have improved current diagnostics and management of metabolic associated fatty liver disease (MAFLD) patients by liver biopsy and therapeutic intervention, yet the deficiency of biomarker spectrum for dissecting subtypes largely hinders the symptomatic treatment. We originally enriched serum from peripheral blood of 618 healthy donors (HD) and 580 MAFLD (400 NAFL, 180 NASH) patients according to multiple clinicopathological indicators. Microarray profiling and qRT-PCR were conducted to identify lncRNAs as candidate biomarkers of MAFLD. Then, we analyzed the matching score of the indicated lncRNA with CAP or MAFLD-associated pathological parameters as well. Additionally, we took advantage of interaction network together with gene expression profiling analysis to further explore the underlying target genes of the identified lncRNA. Herein, we found CAP in nearly all of the NAFL (399/400) and NASH (179/180) patients was higher than that in the HDs (611/618). The differentially expressed lncRNAs were involved in multiple metabolic or immunologic processes by regulating MAFLD-associated pathways. Of them, serum lncPRYP4-3 was identified as a novel candidate biomarker of MAFLD, which was further confirmed by correlation analysis with clinical indicators. Thereafter, we deduced PRS4Y2 was a candidate target of lncPRYP4-3 and mediated the dysfunction in NAFL and NASH patients. Serum lncPRYP4-3 served as a novel biomarker of MAFLD and helped distinguish the subtypes and benefit precise intervention therapy. Our findings also provided overwhelming new evidence for the alteration in biological processes and gene ontology in MAFLD patients.

The Potential Role of PKA/CREB Signaling Pathway Concerned with Gastrodin Administration on Methamphetamine-Induced Conditioned Place Preference Rats and SH-SY5Y Cell Line.

To investigate the effects of gastrodin (GAS) on methamphetamine (MA)-induced conditioned place preference (CPP) in rats and explore its potential mechanisms. MA (10 mg/kg) was initially injected intraperitoneally (i.p.) in rats, after which they were administered either MA or saline alternately from day 4 to 13 (D4-13) for 10 days, followed by treatment with GAS (10 or 20 mg/kg, i.p.) on D15-21 for 7 days. The rats underwent CPP testing after MA and GAS treatment. In vitro, SH-SY5Y cells were exposed to MA (2.0 mM) for 24 h, followed by treatment with GAS (2.0 or 4.0 mM) for 24 h. The expression levels of PKA, P-PKA, CREB, and P-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of MA-induced CPP rats and in SH-SY5Y cells were detected by Western blot analysis. The MA-induced CPP rat model was successfully established. The administration of MA stimulated a significant alteration in behavior, as measured by the CPP protocol. After treatment with GAS, the amount of time rats spent in the MA-paired chamber was significantly reduced. Results also showed that MA increased the expression levels of PKA, P-PKA, CREB, and p-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of CPP rats and in SH-SY5Y cells (p < 0.05). GAS attenuated the effect of MA-induced CPP in rats and decreased the expression levels of proteins in vivo and in vitro. Our study suggests that GAS can attenuate the effects of MA-induced CPP in rats by regulating the PKA/CREB signaling pathway.

[Role of nuclear factor-kappaB in apoptosis pathway of HUVEC].

AIM: To investigate the role of nuclear factor-kappaB in apoptosis pathway of HUVEC. METHODS: The cell lines of HUVEC cultured in vitro were divided into three groups: normal control group, Ang II group, and Gliotoxin group. We investigated the effects of Ang II (0.01 micromol/L, 0.1 micromol/L, 1 micromol/L and 10 micromol/L) on the viability of HUVEC with modified MTT. Then agarose gel electrophoresis and flow cytometry were applied to detect the apoptosis of HUVEC. Finally, the nuclear translocation of NF-kappaB subunit p65 was evaluated by immunocytochemistry. RESULTS: The viability of HUVEC decreased significantly after incubated with 10 micromol/L Ang II for 24 hours. The results of DNA agarose gel and flow cytometry showed that 10 micromol/L Ang II induced the apoptosis of HUVEC, and the apoptosis rate was significantlyhigher than normal control group (P < 0.05). 0.1 mg/L Gliotoxin antagonized this effect of Ang II. The results of immunocytochemistry suggested that NF-kappaB was activated in HUVEC induced by 10 micromol/L Ang II. In contrast, Gliotoxin inhibited the activation of NF-kappaB in HUVEC induced by Ang II. CONCLUSION: (1) Ang II can induce the apoptosis of HUVEC, while the inhibitor of NF-kappaB, Gliotoxin, can antagonize the effect of Ang II. (2) NF-kappaB may play an important role in apoptosis pathway of HUVEC induced by Ang II.