Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She responded poorly to frontline treatment and was in danger. Subsequently, she received a salvage treatment with four doses of MSCs, and her symptoms surprisingly improved quickly. After a lung CT scan that presented with a significantly improved infection, she was discharged eventually. Her primary disease was stable after 6 months of follow-up, and no tumor recurrence or progression was observed. MSCs may be an effective treatment for hyperactive inflammation due to their ability related to immunomodulation and tissue repair. Our case suggests a potential value of MSCs for severe pneumonia that is unresponsive to conventional therapy after a COVID-19 infection. However, unless the situation is urgent, it needs to be considered with caution for patients with tumors. The safety in tumor patients still needs to be observed.

Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis.

AIM: To investigate matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression during the progress of fusarium solani (F.solani) keratitis in a rat model. METHODS: A rat model of F.solani keratitis was produced using corneal scarification and a hand-made contact lens. MMPs and TIMPs expressiond were explored in this rat model of F.solani keratitis using real-time polymerase chain reaction (PCR) and DIF. GM6001 (400 µmol/mL) was used to treat infected corneas. The keratitis duration, amount and area of corneal neovascularization (CNV) were evaluated. RESULTS: MMP-3 expression was 66.3 times higher in infected corneas compared to normal corneas. MMP-8, -9, and -13 expressions were significantly upregulated in the mid-period of the infection, with infected-to-normal ratios of 4.03, 39.86, and 5.94, respectively. MMP-2 and -7 expressions increased in the late period, with the infected-to-normal ratios of 5.94 and 16.22, respectively. TIMP-1 expression was upregulated in the early period, and it was 43.17 times higher in infected compared to normal corneas, but TIMP-2, -3, and -4 expressions were mildly downregulated or unchanged. The results of DIF were consistent with the result of real-time PCR. GM6001, a MMPs inhibitor, decreased the duration of F.solani infection and the amount and area of CNV. CONCLUSION: MMPs and TIMPs contributed into the progress of F.solani keratitis.

MiR-21a-5p suppresses bisphenol A-induced pre-adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK.

Childhood obesity is a metabolic disease characterized by accumulation of excessive fat. Bisphenol A (BPA), a potential obesogen compound, possesses an estrogen mimetic activity and endocrine disruption effect. MicroRNA-21a-5p (miR-21a-5p) is reported to regulate the adipogenic differentiation. Our study showed that miR-21a-5p overexpression significantly decreased the red lipid droplets and triglyceride level in BPA-induced 3T3-L1 cells. BPA induced the mRNA and protein expression levels of PPARγ, C/EBPα and adiponectin, and the induction was inhibited by miR-21a-5p mimics transfection. MiR-21a-5p mimics inhibited the GR activity, GR phosphorylation (S220, S21a-5p2, and S234), and the activation of p38/MAPK pathway, which are elevated by BPA treatment in 3T3-L1 cells. MiR-21a-5p overexpression inhibited the protein level of MKK3, but not in the mRNA level. Luciferase activity assay showed that miR-21a-5p directly targeted map2k3 3'-UTR. MKK3 overexpression attenuated the effect of miR-21a-5p mimics transfection on 3T3-L1 differentiation. We also assessed the body weight, fat mass and the content of serum lipid in rats subcutaneous injected with BPA and miR-21a-5p mimics. MiR-21a-5p overexpression attenuated BPA-induced obesity in vivo. These findings suggested that miR-21a-5p inhibited BPA induced adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK in 3T3-L1 cells, providing a potential therapeutic strategy for BPA induced obesity.

Putative rabbit conjunctival epithelial stem/progenitor cells preferentially reside in palpebral conjunctiva.

PURPOSE: Conjunctival epithelia play an important role in forming a physical protective barrier of the ocular surface. To protect the integrity of the ocular surface, the conjunctival epithelial cells (CECs) must be self-renewing from local stem cells. In this study, the distribution of conjunctival epithelial stem/progenitor cells was determined. METHODS: In a long-term bromodeoxyuridine (BrdU) label-retaining study, adult New Zealand white rabbits were injected intraperitoneally with BrdU 50 mg/kg/d for 7 days and follow-up for 6 weeks. In the short-term BrdU label-retaining study, rabbits were injected intraperitoneally with BrdU 50 mg/kg once and BrdU-labeled CECs were detected after 1, 3, 5, and 7 days, respectively. In vitro, growth kinetics, proliferating cell nuclear antigen (PCNA) immunocytochemical staining and colony-forming abilities of rabbit palpebral, fornical and bulbar CECs cultured in an identical environment were investigated and compared between different parts. RESULTS: In the long-term BrdU label-retaining study, BrdU-labeled cells concentrated at the mucocutaneous junction. In the short-term BrdU label-retaining study, the peak concentration of BrdU label-retaining conjunctival epithelial cells progressively migrated from the mucocutaneous junction to the fornix in rabbits 1, 3, 5 and 7 days postinjection respectively, but a focus of BrdU-labeled cells remained in the mucocutaneous junction at all postinjection intervals. Rabbit palpebral CECs grew faster and assigned more PCNA-positive cells and higher colony-forming abilities than the other two parts in vitro. CONCLUSIONS: Long-term retention of BrdU-labeled cells at the mucocutaneous junction indicated that slow-cycling stem cells may locate at this position. The epithelial stem/progenitor cells at the mucocutaneous junction may serve as an origination of transient amplifying cells that migrate towards the fornix. Rabbit palpebral CECs (including mucocutaneous junction epithelial cells) possess higher self-renewing ability in vitro. Collectively, conjunctival epithelial stem/progenitor cells in the rabbit may preferentially reside in palpebral conjunctiva, especially the mucocutaneous junction.