Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.

Objective:To evaluate the effect of berberine on the volume and weight of, cell proliferation and apoptosis in transplanted cutaneous squamous cell carcinoma (cSCC) in nude mice inoculated with A431 cells, and to explore the possible mechanism underlying the inhibitory effect of berberine on cSCC.Methods:A431 cells were cultured, and A431 cell suspension was subcutaneously injected into the back of 20 nude mice to establish a nude mouse model of transplanted cSCC. On day 15 after inoculation, these tumor-bearing mice were randomly and equally divided into 4 groups: low-, medium- and high-dose berberine groups intraperitoneally injected with 10, 20 and 25 mg/kg berberine solution respectively, and control group intraperitoneally injected with sodium chloride physiological solution. The treatment was performed once a day for 35 consecutive days. The tumor volume was measured before, and on days 7, 14, 21, 28 and 35 after the start of treatment. After the end of the experiment, the nude mice were sacrificed, and the tumors were removed and weighed to calculate the tumor growth inhibition rate. Histopathological examination was performed in these transplanted tumors, immunohistochemical study was conducted to determine the expression of Ki67, TUNNEL staining was conducted to determine the number of apoptotic cells in the transplanted tumor tissues, fluorescence-based quantitative PCR and Western blot analysis were employed to determine the mRNA and protein expression of apoptosis-related proteins Bax, Bcl-2, caspase-3 and Ezrin respectively. One-way analysis of variance was used for comparisons among multiple groups, and Dunnett- t test for comparisons of each berberine group with the control group. Results:Along with the increase in the dose of berberine and treatment duration, the tumor growth curve gradually became flat, the tumor growth was inhibited to different degrees in the berberine groups, and the high-dose berberine showed the strongest inhibitory effect on the tumor growth. The tumor growth inhibition rate was 31.05%, 66.68%, 76.49% in the low-, medium-, and high-dose berberine groups respectively, and the tumor weight was significantly lower in the 3 berberine groups than in the control group ( t = 4.07, 6.33, 7.26, respectively, all P < 0.01) . Along with the increase in the dose of berberine, histopathological examination of the transplanted tumors showed that the extent and area of tumor cell necrosis increased, while immunohistochemical study showed that the number of Ki67-positive cells gradually decreased. Moreover, the number of Ki67-positive cells was significantly lower in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) , but the number of apoptotic cells was significantly higher in the berberine groups than in the control group ( P < 0.05 or < 0.01) . The mRNA and protein expression of Bax, Bcl-2, caspase-3 and Ezrin significantly differed among the 4 groups (all P < 0.01) . In addition, the mRNA expression of Bcl-2 was significantly lower in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) , and the protein expression of Bcl-2 was significantly lower in the medium- and high-dose berberine groups than in the control group (both P < 0.01) ; Bax mRNA expression in the high-dose berberine group and caspase-3 mRNA expression in the medium- and high-dose berberine groups were significantly higher than the corresponding mRNAs in the control group respectively ( P < 0.05 or < 0.01) , and the protein expression of Bax and caspase-3 was significantly higher in the low-, medium- and high-dose berberine groups than in the control group (all P < 0.01) ; Ezrin mRNA expression was significantly higher in the high-dose berberine group than in the control group ( P < 0.01) , but its protein expression was significantly lower in the low-, medium-, and high-dose berberine groups than in the control group (all P < 0.01) . Conclusion:Berberine can inhibit the proliferation of A431 cells and promote their apoptosis in the transplanted cSCC of the nude mice, and then suppress the growth of transplanted cSCC in the nude mice to a certain extent, which may be related to the upregulation of Bax and caspase-3 and downregulation of Bcl-2 and Ezrin.

To explore the prevalence of hepatitis B virus (HBV) in multiple myeloma (MM) patients, as well as to compare the clinical characteristics and outcome between HBV infected and non-HBV infected patients. Methods:The serology markers of HBV were detected in 363 MM patients and 11227 cases of healthy controls through chemiluminescence. HBV-DNA was measured via real-time quantitative chain reaction. Results:Sixteen out of 363 MM patients (4.4%) were HBsAg-positive, showing significant difference with healthy controls (2.4%). No statistically significant differences were observed in terms of sex, age, type of monoclonal (M) protein, International Staging System (ISS) stage, stem cell transplantation, and risk stratification between HBsAg-positive and HBsAg-negative patients. No significant effect of HBV infection was found on the OS of MM patients. HBV reactivation was observed in two HBsAg-positive MM patients who were treated with combination chemotherapy, including bortezomib and dexamethasone. The replication of HBV could be inhibited by anti-HBV drugs. Conclusion:A higher prevalence of HBV infection was revealed in MM patients. Close monitoring of HBV replication should be conducted in MM patients with HBV infection before and during the courses of chemotherapy.