Microplastics (MPs) and nanoplastics (NPs) are emergent pollutants, which have sparked widespread concern. They can infiltrate the body via ingestion, inhalation, and cutaneous contact. As such, there is a general worry that MPs/NPs may have an impact on human health in addition to the environmental issues they engender. The threat of MPs/NPs to the liver, gastrointestinal system, and inflammatory levels have been thoroughly documented in the previous research. With the detection of MPs/NPs in fetal compartment and the prevalence of infertility, an increasing number of studies have put an emphasis on their reproductive toxicity in female. Moreover, MPs/NPs have the potential to interact with other contaminants, thus enhancing or diminishing the combined toxicity. This review summarizes the deleterious effects of MPs/NPs and co-exposure with other pollutants on female throughout the reproduction period of various species, spanning from reproductive failure to cross-generational developmental disorders in progenies. Although these impacts may not be directly extrapolated to humans, they do provide a framework for evaluating the potential mechanisms underlying the reproductive toxicity of MPs/NPs.

About 95% of Glioblastoma (GBM) patients experience tumor relapse as a consequence of resistance to the first-line standard chemotherapy using temozolomide (TMZ). Recent studies reported consistently elevated expression levels of carbonic anhydrase CA2 in recurrent glioblastoma and temozolomide-resistant glioblastoma stem-like cells (GSCs). Here we show that CA2 is preferentially expressed in GSCs and upregulated by TMZ treatment. When expressed in GBM cell lines, CA2 exerts significant metabolic changes reflected by enhanced oxygen consumption and increased extracellular acidification causing higher rates of cell invasion. Notably, GBM cells expressing CA2 respond to combined treatment with TMZ and brinzolamide (BRZ), a non-toxic and potent CA2 inhibitor. Interestingly, brinzolamide was more effective than the pan-CA inhibitor Acetazolamide (ACZ) to sensitize naïve GSCs and TMZ-resistant GSCs to TMZ induced cell death. Mechanistically, we demonstrated that the combined treatment of GBM stem cells with TMZ and BRZ caused autophagy of GBM cell lines and GSCs, reflected by enhanced LC3 cleavage (LC3-II) and p62 reduction. Our findings illustrate the potential of CA2 as a chemo-sensitizing drug target in recurrent GBM and propose a combined treatment of TMZ with CA2 inhibitor to tackle GBM chemoresistance and recurrence.

Objective: Pituitary adenomas (PAs) can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation. Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo. However, the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear. Methods: Target gene prediction and transcriptomic profiling of invasive vs. noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14. For cellular analyses of miRNA functions, two mouse PA cell lines (AtT20 and TtT/GF) were transfected with miR-149-3p and miR-149-5p, respectively. The effects of miR-149 (3p and 5p) on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays, scratch migration assays, and invasion assays. Results: A significant downregulation of miRNA-149 was observed in invasive vs. noninvasive PA (0.32 vs. 0.09, P<0.0001). In AtT-20 and TtT/GF mouse PAs cells, transfection of mimic miRNA-149 (3p and 5p) caused a significantly reduced cell proliferation and matrigel invasion, whilst the effect on cell migration was less pronounced. Both strands of miRNA-149 (3p and 5p) markedly reduced protein levels of ADAM12 and MMP-14 by at least 40% in both cell lines. Conclusion: This study proved that the invasiveness of PA cells is, at least partly, regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.

This study evaluated the therapeutic effects of surgical treatment of cystic pituitary prolactin-secreting macroadenomas. The clinical data of 42 patients with cystic pituitary prolactin-secreting macroadenomas were retrospectively analyzed. Patients were divided into medication plus surgery and surgery alone groups based on the regularity of bromocriptine treatment before surgery. Both groups underwent extra-pseudocapsular transsphenoidal surgery for tumor resection, and postoperative images and clinical follow-up were retrospectively reviewed. We also evaluated patients who opted for long-term treatment with bromocriptine. In the medication plus surgery group, the long-term surgical cure rate and comprehensive remission rate were 33.3% and 41.7%, while in the surgery alone group they were 69.2% and 80.8%, respectively. No severe or permanent complications occurred, and the surgical complication morbidity rate was 10.5%. The rate of tumor progression during the long-term follow-up was 33.3% and 7.7% in the medication plus surgery and surgery alone groups, respectively. The time required for prolactin levels to return to normal in the surgery alone group was significantly faster and the proportion that returned to normal was significantly higher. Direct surgical treatment after diagnosis combined with postoperative individualized bromocriptine adjuvant therapy had better efficacy in patients with cystic pituitary prolactin-secreting macroadenomas, but its long-term effectiveness requires further follow-up.