PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma

AIM:To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL)patients,and explore its associations with patients’clinical parameters.METHODS:Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained,and 30 lymphoid tissue samples from reactive lymph nodes of age-and sexmatched patients represented control samples.Staging and diagnostic procedures were conducted according to the Lugano staging system.All patients had been treated with three therapeutic modalities:surgery,chemotherapy,or radiotherapy.Expression of MYC and BCL-2 were detected at both protein and m RNA levels by immunohistochemistry and real-time RT-PCR.RESULTS:Positive expression levels of MYC and BCL-2proteins were detected in 35%and 45%of patients,respectively.MYC+/BCL-2+protein was present in30%of patients.MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 m RNA expression,respectively(both P<0.05).We found that advancedstage disease(atⅡE-Ⅳ)was associated with MYC and BCL-2 coexpression levels(P<0.05).In addition,MYC+/BCL-2+patients had more difficulty in achieving complete remission than others(P<0.05).Presenceof MYC protein expression only affected overall survivaland progression-free survival(PFS)when BCL-2 proteinwas coexpressed.The adverse prognostic impact ofMYC+/BCL-2+protein on PFS remained significant(P<0.05)even after adjusting for age,Lugano stage,international prognostic index,and BCL-2 proteinexpression in a multivariable model.CONCLUSION:MYC+/BCL-2+patients have worsechemotherapy response and poorer prognosis thanpatients who only express one of the two proteins,suggesting that assessment of MYC and BCL-2 expressionby immunohistochemistry has clinical significance inpredicting clinical outcomes of PGI-DLBCL patients.