Aims Sepsis-associated acute kidney injury (S-AKI) is a severe complication of sepsis, characterized by high morbidity and mortality, yet lacks effective treatment options in clinical practice. This study aims to investigate the role of SIRT2 in mediating renal injury and inflammation in S-AKI. Materials and methods LPS-induced S-AKI models were established in wild-type and SIRT2 whole-body knockout mice, as well as in HK-2 cells with SIRT2 knockdown or overexpression. Renal injury, inflammatory cytokines, macrophage infiltration, and cell death were evaluated by histological, biochemical, and molecular analyses. NEU1 acetylation, sialidase activity, CD44 sialylation, and downstream PI3K/AKT signaling were further examined. Pharmacological inhibition studies in mice were performed using SIRT2 selective inhibitor AGK2 and a nano-formulation of AGK2 (Nano-AGK2). Key findings We found that SIRT2 whole-body knockout significantly alleviated renal damage and reduced pro-inflammatory cytokines in S-AKI. Knockdown of SIRT2 attenuated LPS-induced inflammation and cell death in HK-2 cells, whereas its overexpression exacerbated the inflammatory response and cell death. Mechanistically, SIRT2 was shown to deacetylate NEU1 at lysine 395. Inhibiting SIRT2 caused hyperacetylated NEU1, which reduced NEU1 sialidase activity and enhanced CD44 sialylation and CD44/HA binding, promoting PI3K/AKT signaling and renal protection. Furthermore, pharmacological inhibition using AGK2 mitigated LPS-induced renal injury and inflammation, while Nano-AGK2 exhibited enhanced renal accumulation and therapeutic efficacy compared to free AGK2. Significance These findings identify SIRT2 as a novel post-translational regulator in S-AKI, suggesting that SIRT2 inhibition may serve as a potential therapeutic target for S-AKI, which deserves further preclinical investigation.

Aim:Acute leukemia (AL) during pregnancy is a rare condition with limited evidence-based information available on the management. The study aims to analyze the pregnancy and fetal outcomes of pregnant women with acute leukemia diagnosed during pregnancy. Methods:In this retrospective study, 18 pregnant women who were diagnosed with AL during pregnancy from January 2013 to January 2024 were reviewed. Results:Of these patients, 6 delivered before chemotherapy while 12 received chemotherapy after induced abortion. Six fetus were born through spontaneous delivery or cesarean section, and one died 3 days after birth. Fourteen patients (77.8%) were found to have decreased platelets by full blood count test. The delivery group had a longer gestational age, longer time from pregnancy termination to chemotherapy compared to the abortion group. The median age of the rest 5 newborns was 32 months. Five newborns were healthy without any deformities or developmental issues. With a median follow-up of 3 years, the overall survival (OS) rates for 18 patients with acute leukemia were estimated at 88.2%. Patients in the delivery group had a significantly lower OS rate compared to those in abortion group. Overall, starting chemotherapy as soon as possible can improve OS rates for pregnant women with AL. Conclusion:Collectively, we suggest that for pregnant patients diagnosed in early or late stages of pregnancy (after 30 weeks), opting for termination of pregnancy before starting chemotherapy could lead to better outcomes for the mothers.

Exposure to fine particulate matter (PM2.5) represents a critical environmental health threat, with growing evidence linking it to accelerated chronic kidney disease (CKD) progression. However, the underlying mechanism of this toxicity remains poorly understood. This study investigated whether PM2.5 exposure induces renal tubular cell senescence and explored the molecular basis of this process. We found that PM2.5 exposure caused kidney injury in mice and upregulated senescence markers in both mice and human kidney proximal tubule epithelial (HK-2) cells. Mechanistically, PM2.5 downregulated FOXP1 expression, relieving its transcriptional repression of CDKN1A (encoding P21), leading to P21 upregulation and subsequent cell cycle arrest. Overexpressing FOXP1 or treating with quercetin mitigated PM2.5-induced senescence in HK-2 cells. Our findings demonstrate that reduced FOXP1 drives cellular senescence in PM2.5-induced renal injury and identify quercetin as a potential therapeutic agent that activates FOXP1 and alleviates PM2.5 nephrotoxicity.

Type VII secretion systems (T7SS) are increasingly recognized as pivotal for bacterial adaptation across both environmental and host-associated niches in Gram-positive bacteria. Although T7SS has been reported to contribute to iron acquisition, the possibility of an active, more targeted iron uptake mechanism remains underexplored. Here, we reveal a distinct, active T7SS-mediated iron import mechanism in Corynebacterium glutamicum. We show that T7SS expression is induced under iron limitation and oxidative stress conditions and is tightly regulated by the ferric uptake regulator (Fur) to benefit bacterial survival. Surprisingly, this iron uptake pathway relies on the T7SS-secreted effector ExsI, an iron-binding protein that collaborates with the membrane receptor ExiR to facilitate iron uptake into the cytoplasm. This ExsI-ExiR-mediated active iron acquisition mechanism enhances bacterial oxidative stress resistance and confers a competitive advantage in iron-limited environments. Furthermore, we show that ExsI homologs in Mycobacterium smegmatis circumvent calprotectin-mediated nutritional immunity, extending the relevance of this mechanism to host-pathogen interactions. Taken together, our data demonstrate a key role for T7SS in orchestrating active iron uptake, oxidative stress resilience, competitive fitness, and evasion of host nutritional immunity, highlighting its significant role in bacterial physiology and host-pathogen interactions.IMPORTANCEType VII secretion systems (T7SS) are increasingly recognized as an indispensable secretion system for Gram-positive bacteria, mediating processes vital for bacterial survival and pathogenesis. This work reveals a previously unrecognized mode of active iron acquisition mediated by T7SS, which not only boosts oxidative stress resistance in Corynebacterium glutamicum but also provides a competitive edge under nutrient-limited conditions. ExsI homologs in Mycobacterium smegmatis overcome calprotectin-mediated iron withholding, suggesting that T7SS-driven iron acquisition extends to immune evasion. These uncovered previously unreported functions of T7SS emphasize the indispensable importance of T7SS in bacterial physiology, enhancing our understanding of T7SS.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse lung inflammation and edema, with diffuse alveolar damage as the hallmark pathology. Paxillin plays a crucial role in the signaling pathways that regulate inflammatory responses. However, its involvement in modulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and its impact on lung epithelial integrity remain largely unexplored. Hematoxylin and eosin staining, immunohistochemistry, and Western blot (WB) analysis were performed. In the present study, lipopolysaccharide (LPS) stimulation significantly upregulated paxillin expression and phosphorylation concomitant with NLRP3 inflammasome activation. Co-immunoprecipitation was performed to assess the interaction between paxillin and NLRP3. To further explore the role of paxillin, a lentiviral knockdown approach was used to downregulate its expression. Paxillin knockdown attenuated the NLRP3 inflammasome-mediated inflammatory response in LPS-induced ALI/ARDS, leading to enhanced epithelial cell migration and improved wound healing capacity. In conclusion, paxillin plays a key role in regulating inflammation mediated by NLRP3 inflammasome. Overall, suppression of Paxillin expression provides protection by alleviating LPS-induced inflammation and promoting epithelial repair, thus highlighting its potential as a therapeutic target for ALI/ARDS.

Ferroptosis, a recently identified form of regulated cell death, is characterized by lipid peroxidation and iron accumulation, plays a critical role in early brain injury after subarachnoid hemorrhage. Ginsenoside Rd, an active compound isolated from ginseng, is known for its neuroprotective properties. However, its influence on SAH-induced ferroptosis remains unclear. In this study, we constructed an SAH model using intravascular perforation in vivo and treated HT22 cells with oxyhemoglobin to simulate the condition in vitro. We observed significant changes in ferroptosis markers, including GPX4 and ACSL4, following SAH. Administration of ginsenoside Rd to both rats and HT22 cells effectively inhibited neuronal ferroptosis induced by SAH, alleviating neurological deficits and cognitive dysfunction in rats. Notably, the neuroprotective properties of ginsenoside Rd were countered by the STING pathway agonist 2’3’-cGAMP. Experiments conducted in vitro and in vivo illustrated that the impacts of ginsenoside Rd were counteracted by the BQR inhibitor. Our findings suggest that ginsenoside Rd mitigates EBI after SAH by suppressing neuronal ferroptosis through the cGAS/STING pathway while upregulating DHODH levels. These outcomes emphasize the potential of ginsenoside Rd as a therapeutic candidate for subarachnoid hemorrhage.

Diabetic nephropathy (DN) is a serious complication of diabetes, and inflammation plays a crucial role. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, which is involved in the regulation of cell metabolism, proliferation and longevity through deacetylation. Our previous research showed a positive correlation between urinary SIRT2 levels and renal injury markers in DN patients. Therefore, this study explored the specific role of SIRT2 in DN and its regulatory relationship with inflammatory response. Increased expression of SIRT2 was observed in kidney tissues of DN mice and in HK2 cells induced by HG/PA. SIRT2 knockout mice alleviated microalbuminuria, inflammatory responses, and kidney damage induced by HFD/STZ. In HK2 cells, reducing SIRT2 expression or inhibiting its acetylase activity alleviated the inflammatory response induced by HG/PA, whereas overexpression of SIRT2 exacerbated this response. Further investigation revealed that SIRT2 directly interacts with c-Jun/c-Fos, promoting their deacetylation. And inhibitors of c-Jun/c-Fos partially reversed the upregulation of inflammatory factors caused by SIRT2 overexpression. Meanwhile, disrupting SIRT2 reduced the binding activity between AP-1 and the MCP-1 promoter, while overexpressing SIRT2 further increased their binding activity in HK2 cells. Interestingly, SIRT2 increased its phosphorylation while deacetylating c-Jun, leading to nuclear accumulation of p-c-Jun. In conclusion, SIRT2 knockout can alleviate kidney injury and inflammatory response in HFD/STZ mice. The mechanism is related to the increased acetylation of c-Jun/c-Fos in renal tubular epithelial cells, accompanied by crosstalk between c-Jun phosphorylation and acetylation. Blocking SIRT2 could therefore be a potential therapeutic target for DN.

To study the neuronal protective effect and its potential mechanism of C16 against gp120-induced cognitive impairment in vitro and in vivo. The NORT method was used to evaluate the short-term memory abilities of rats, the morphological changes in hippocampus were observed by Nissl staining. Cell viability and damage degree were detected by MTT and LDH. The cell living/apoptosis status of PC12 cells was determined by AO/EB double staining and the relative mRNA expressions of PKR, IRE1α, JNK, GRP78, and CHOP were detected by RT-qPCR. In comparison with the gp120 + Memantine and gp120 + C16 groups, the rats in the gp120 group showed a significantly decreased discrimination index (P < 0.001), with disordered CA1 region cells and reduced neuron numbers. AO/EB double staining revealed morphological changes in the gp120 and NMDA groups, while cells in the gp120 + C16 and NMDA + C16 groups resembled the control group. And C16 can significantly down-regulate the mRNA expression levels of PKR, IRE1α, JNK, GRP78, and CHOP. (P < 0.05). C16 can reduce the cognitive impairment stimulated by gp120 or NMDA, the protective mechanism may be correlated with inhibiting the upregulation of PKR/IRE1α/JNK pathway and suppressing apoptosis induced by downstream proteins GRP78 and CHOP.

Objectives Asthma, a prevalent chronic disease, poses significant health threats and burdens healthcare systems. This study focused on the role of bronchial epithelial cells in asthma pathophysiology.Methods Bioinformatics was used to identify key asthmarelated genes. An ovalbumin-sensitized mouse model and an IL-13-stimulated Beas-2B cell model were established for further investigation.Results Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a crucial gene in asthma. CEACAM5 expression was elevated in asthmatic mouse lung tissues and IL-13-stimulated Beas-2B cells, primarily in bronchial epithelial cells. CEACAM5 induced reactive oxygen species (ROS), lipid peroxidation, and ferroptosis. Interfering with CEACAM5 reduced ROS, malondialdehyde levels, and enhanced antioxidant capacity, while inhibiting iron accumulation and autophagy. Overexpression of CEACAM5 in IL-13-stimulated cells activated the JAK/STAT6 pathway, which was necessary for CEACAM5-induced autophagy, ROS accumulation, lipid peroxidation, and ferroptosis.Conclusion CEACAM5 promotes ferroptosis and autophagy in airway epithelial cells via the JAK/STAT6 pathway, exacerbating asthma symptoms. It represents a potential target for clinical treatment.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2h before or 4h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.

Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. The two drugs indicated for IPF have limited efficacy and there is an urgent need to develop new drugs. Thymosin beta 4 (T beta 4) is a natural endogenous repair factor whose antifibrotic effects have been reported. This study aimed to evaluate the effect of exogenous recombinant human thymosin beta 4 (rhT beta 4) on pulmonary fibrosis. Methods: Pulmonary fibrosis was induced in mice with bleomycin, and rhT beta 4 was administrated by nebulization following three strategies: early dosing, mid-term dosing, and late dosing. The rhT beta 4 efficacy was assessed by hydroxyproline, lung function, and lung histopathology. In vitro, the effects of rhT beta 4 on fibroblast and lung epithelial cell phenotypes, as well as the TGF-beta 1 pathway, were evaluated. Key findings: Aerosol administration of rhT beta 4 could alleviate bleomycin-induced pulmonary fibrosis in mice at different stages of fibrosis. Studies conducted in vitro suggested that rhT beta 4 could suppress lung fibroblasts from proliferating, migrating, and activation via regulating the TGF-beta 1 signalling pathway. In vitro, rhT beta 4 also inhibited the epithelial-mesenchymal transition-like process of pulmonary epithelial cells. Conclusions: This study suggests that nebulized rhT beta 4 is a potential treatment for IPF.

Background Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus (DM) with complex pathophysiology and variable clinical presentations. Management can be challenging for a single specialty, so multidisciplinary team (MDT) approaches are recommended for comprehensive care. However, conventional MDT approaches may not meet the requirements of protracted treatment and recovery periods associated with DFUs. This report presents a case of successful MDT management of a Wagner Grade 3 DFU complicated by methicillin-resistant Staphylococcus aureus (MRSA) infection, led by wound care specialists. Methods A 64-year-old man with a DFU on his right foot sought care at a wound center following a thermal injury. Wound care specialists coordinated the involvement of various specialists for collaborative wound management. Plastic surgery specialists performed expert debridement, pharmacists monitored the culture of wound secretions, obtaining culture results including MRSA, and administered targeted treatment with sensitive antibiotics such as piperacillin tazobactam, rifampicin, Vancomycin, and an endocrinologist optimized glycemic control. The wound care team employed negative pressure wound therapy, hyperbaric oxygen therapy, and regular wound debridement and dressing changes as needed. Results After discharge, wound care specialists provided continuous follow-up and appropriate wound care guidance and education. Through wound care nurse-led MDT intervention, spanning two months, the patient's right foot ulcer healed completely and exhibited good recovery. Conclusion Wound care nurse-led MDT intervention can improve care outcomes, reduce recurrent hospitalizations, enhance patient compliance, control blood glucose, promote wound healing, control costs, and maintain patient satisfaction. However, standardized management processes in this context are currently lacking. This case report explores a potential effective care intervention model.

The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle-protrusion-retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal-karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live-born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement.

Background Studies have shown that the release of endogenous glutamate (Glu) participates in lung injury by activating N-methyl-D-aspartate receptor (NMDAR), but the mechanism is still unclear. This study was to investigate the effects and related mechanisms of Glu on the lipid synthesis of pulmonary surfactant (PS) in isolated rat lung tissues. Methods The cultured lung tissues of adult SD rats were treated with Glu. The amount of [3H]-choline incorporation into phosphatidylcholine (PC) was detected. RT-PCR and Western blot were used to detect the changes of mRNA and protein expression of cytidine triphosphate: phosphocholine cytidylyltransferase alpha (CCTα), a key regulatory enzyme in PC biosynthesis. Western blot was used to detect the expression of NMDAR1, which is a functional subunit of NMDAR. Specific protein 1 (Sp1) expression plasmids were used. After transfected with Sp1 expression plasmids, the mRNA and protein levels of CCTα were detected by RT-PCR and Western blot in A549 cells. After treated with NMDA and MK-801, the mRNA and protein levels of Sp1 were detected by RT-PCR and Western blot in A549 cells. Results Glu decreased the incorporation of [3H]-choline into PC in a concentration- and time- dependent manner. Glu treatment significantly reduced the mRNA and protein levels of CCTα in lungs. Glu treatment up-regulated NMDAR1 protein expression, and the NMDAR blocker MK-801 could partially reverse the reduction of [3H]-choline incorporation induced by Glu (10−4 mol/L) in lungs. After transfected with Sp1 plasmid for 30 h, the mRNA and protein expression levels of CCTα were increased and the protein expression of Sp1 was also up-regulated. After A549 cells were treated with NMDA, the level of Sp1 mRNA did not change significantly, but the expression of nucleus protein in Sp1 was significantly decreased, while the expression of cytoplasmic protein was significantly increased. However, MK-801could reverse these changes. Conclusions Glu reduced the biosynthesis of the main lipid PC in PS and inhibited CCTα expression by activating NMDAR, which were mediated by the inhibition of the nuclear translocation of Sp1 and the promoter activity of CCTα. In conclusion, NMDAR-mediated Glu toxicity leading to impaired PS synthesis may be a potential pathogenesis of lung injury.

Ferroptosis, a newly discovered type of regulated cell death, has been implicated in numerous human diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease with poor prognosis and limited treatment options. Emerging evidence has linked ferroptosis and glutamate-determined cell fate which is considered a new light on the etiology of pulmonary fibrosis. Here, we observed that N-methyl d-aspartate receptor (NMDAR) activation promoted cell damage and iron deposition in MLE-12 cells in a dose-, time-, and receptor-dependent manner. This mediated substantial Ca2+ influx, upregulated the expression levels of nNOS and IRP1, and affected intracellular iron homeostasis by regulating the expression of iron transport-related proteins (i.e., TFR1, DMT1, and FPN). Excessive iron load promoted the continuous accumulation of total intracellular and mitochondrial reactive oxygen species, which ultimately led to ferroptosis. NMDAR inhibition reduced lung injury and pulmonary fibrosis in bleomycin-induced mice. Bleomycin stimulation upregulated the expression of NMDAR1, nNOS, and IRP1 in mouse lung tissues, which ultimately led to iron deposition via regulation of the expression of various iron metabolism-related genes. NMDAR activation initiated the pulmonary fibrosis process by inducing iron deposition in lung tissues and ferroptosis of alveolar type II cells. Our data suggest that NMDAR activation regulates the expression of iron metabolism-related genes by promoting calcium influx, increasing nNOS and IRP1 expression, and increasing iron deposition by affecting cellular iron homeostasis, ultimately leading to mitochondrial damage, mitochondrial dysfunction, and ferroptosis. NMDAR activation-induced ferroptosis of alveolar type II cells might be a key event to the initiation of pulmonary fibrosis.

Background and Aims The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Methods Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. Results MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Conclusion Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Mutations in mitochondrial DNA (mtDNA) contribute to a variety of serious multi-organ human diseases, which are strictly inherited from the maternal germline. However, there is currently no curative treatment. Attention has been focused on preventing the transmission of mitochondrial diseases through mitochondrial replacement (MR) therapy, but levels of mutant mtDNA can often unexpectedly undergo significant changes known as mitochondrial genetic drift. Here, we proposed a novel strategy to perform spindle-chromosomal complex transfer (SCCT) with maximal residue removal (MRR) in metaphase II (MII) oocytes, thus hopefully eliminated the transmission of mtDNA diseases. With the MRR procedure, we initially investigated the proportions of mtDNA copy numbers in isolated karyoplasts to those of individual oocytes. Spindle-chromosomal morphology and copy number variation (CNV) analysis also confirmed the safety of this method. Then, we reconstructed oocytes by MRR-SCCT, which well developed to blastocysts with minimal mtDNA residue and normal chromosomal copy numbers. Meanwhile, we optimized the manipulation order between intracytoplasmic sperm injection (ICSI) and SCC transfer and concluded that ICSI-then-transfer was conducive to avoid premature activation of reconstructed oocytes in favor of normal fertilization. Offspring of mice generated by embryos transplantation in vivo and embryonic stem cells derivation further presented evidences for competitive development competence and stable mtDNA carryover without genetic drift. Importantly, we also successfully accomplished SCCT in human MII oocytes resulting in tiny mtDNA residue and excellent embryo development through MRR manipulation. Taken together, our preclinical mouse and human models of the MRR-SCCT strategy not only demonstrated efficient residue removal but also high compatibility with normal embryo development, thus could potentially be served as a feasible clinical treatment to prevent the transmission of inherited mtDNA diseases.