Sheng Wu Gong Cheng Xue Bao. 2023 Feb 25;39(2):614-624. doi: 10.13345/j.cjb.220644.

ABSTRACT

Papaya, which is mainly cultivated in the southeastern region of China, is one of the four famous fruits in Lingnan. It is favored by people because of its edible and medicinal value. Fructose-6-phosphate, 2-kinase/fructose-2, 6-bisphosphatase (F2KP) is a unique bifunctional enzyme with a kinase domain and an esterase domain that catalyzes the synthesis and degradation of fructose-2, 6-bisphosphate (Fru-2, 6-P2), an important regulator of glucose metabolism in organisms. In order to study the function of the gene CpF2KP encoding the enzyme in papaya, it is particularly important to obtain the target protein. In this study, the coding sequence (CDS) of CpF2KP, with a full-length of 2 274 bp, was got from the papaya genome. The amplified sequence of full-length CDS was cloned into the vector PGEX-4T-1 which was double digested with EcoR I and BamH I. The amplified sequence was constructed into a prokaryotic expression vector by genetic recombination. After exploring the induction conditions, the results of SDS-PAGE showed that the size of the recombinant GST-CpF2KP protein was about 110 kDa. The optimum IPTG concentration and temperature for CpF2KP induction were 0.5 mmol/L and 28 ℃, respectively. The purified sin[A1] gle target protein was obtained after purifying the induced CpF2KP protein. In addition, the expression level of this gene was detected in different tissues, and showed that the gene was expressed at the highest level in seeds and the lowest in pulp. This study provides an important basis for further revealing the function of CpF2KP protein and studying the involved biological processes of this gene in papaya.

PMID:36847093 | DOI:10.13345/j.cjb.220644

Development. 2023 Feb 27:dev.201163. doi: 10.1242/dev.201163. Online ahead of print.

ABSTRACT

The regenerative capacity of the mammalian heart is poor with one potential reason being that adult cardiomyocytes cannot proliferate at sufficient levels to replace lost tissue. During development and neonatal stages, cardiomyocytes can successfully divide under injury conditions; however, as these cells mature their ability to proliferate is lost. Therefore, understanding regulatory programs that can induce post-mitotic cardiomyocytes into a proliferative state is essential to enhance cardiac regeneration. Here we report the forkhead transcription factor, foxm1, is required for cardiomyocyte proliferation after injury through transcriptional regulation of cell cycle genes. Transcriptomic analysis of injured zebrafish hearts revealed that foxm1 expression is increased in border zone cardiomyocytes. Decreased cardiomyocyte proliferation and expression of cell cycle genes in foxm1 mutant hearts was observed, suggesting it is required for cell cycle checkpoints. Subsequent analysis of a candidate Foxm1 target gene, cenpf, revealed this microtubule and kinetochore binding protein is also required for cardiac regeneration. Moreover, cenpf mutants show increased cardiomyocyte binucleation. Thus, foxm1 and cenpf are required for cardiomyocytes to complete mitosis during zebrafish cardiac regeneration.

PMID:36846912 | DOI:10.1242/dev.201163

Virus Evol. 2023 Jan 27;9(1):vead008. doi: 10.1093/ve/vead008. eCollection 2023.

ABSTRACT

The burden of ticks and the pathogens they carry is increasing worldwide. Powassan virus (POWV; Flaviviridae: Flavivirus), the only known North American tick-borne flavivirus, is of particular concern due to rising cases and the severe morbidity of POWV encephalitis. Here, we use a multifaceted approach to evaluate the emergence of the II POWV lineage, known as deer tick virus (DTV), in parts of North America where human cases occur. We detected DTV-positive ticks from eight of twenty locations in the Northeast USA with an average infection rate of 1.4 per cent. High-depth, whole-genome sequencing of eighty-four POWV and DTV samples allowed us to assess geographic and temporal phylodynamics. We observed both stable infection in the Northeast USA and patterns of geographic dispersal within and between regions. A Bayesian skyline analysis demonstrated DTV population expansion over the last 50 years. This is concordant with the documented expansion of Ixodes scapularis tick populations and suggests an increasing risk of human exposure as the vector spreads. Finally, we isolated sixteen novel viruses in cell culture and demonstrated limited genetic change after passage, a valuable resource for future studies investigating this emerging virus.

PMID:36846826 | PMC:PMC9943884 | DOI:10.1093/ve/vead008

Front Microbiol. 2023 Feb 8;14:1113442. doi: 10.3389/fmicb.2023.1113442. eCollection 2023.

ABSTRACT

The type III secretion system (T3SS) is a well-studied pathogenicity determinant of many bacteria through which effectors (T3Es) are translocated into the host cell, where they exercise a wide range of functions to deceive the host cell's immunity and to establish a niche. Here we look at the different approaches that are used to functionally characterize a T3E. Such approaches include host localization studies, virulence screenings, biochemical activity assays, and large-scale omics, such as transcriptomics, interactomics, and metabolomics, among others. By means of the phytopathogenic Ralstonia solanacearum species complex (RSSC) as a case study, the current advances of these methods will be explored, alongside the progress made in understanding effector biology. Data obtained by such complementary methods provide crucial information to comprehend the entire function of the effectome and will eventually lead to a better understanding of the phytopathogen, opening opportunities to tackle it.

PMID:36846751 | PMC:PMC9945535 | DOI:10.3389/fmicb.2023.1113442

Oxid Med Cell Longev. 2023 Feb 17;2023:1649842. doi: 10.1155/2023/1649842. eCollection 2023.

ABSTRACT

Traumatic brain injury (TBI), a kind of external trauma-induced brain function alteration, has posed a financial burden on the public health system. TBI pathogenesis involves a complicated set of events, including primary and secondary injuries that can cause mitochondrial damage. Mitophagy, a process in which defective mitochondria are specifically degraded, segregates and degrades defective mitochondria allowing a healthier mitochondrial network. Mitophagy ensures that mitochondria remain healthy during TBI, determining whether neurons live or die. Mitophagy acts as a critical regulator in maintaining neuronal survival and healthy. This review will discuss the TBI pathophysiology and the consequences of the damage it causes to mitochondria. This review article will explore the mitophagy process, its key factors, and pathways and reveal the role of mitophagy in TBI. Mitophagy will be further recognized as a therapeutic approach in TBI. This review will offer new insights into mitophagy's role in TBI progression.

PMID:36846712 | PMC:PMC9957633 | DOI:10.1155/2023/1649842

Front Neurosci. 2023 Feb 9;17:1041433. doi: 10.3389/fnins.2023.1041433. eCollection 2023.

ABSTRACT

Precision psychiatry has emerged as part of the shift to personalized medicine and builds on frameworks such as the U.S. National Institute of Mental Health Research Domain Criteria (RDoC), multilevel biological "omics" data and, most recently, computational psychiatry. The shift is prompted by the realization that a one-size-fits all approach is inadequate to guide clinical care because people differ in ways that are not captured by broad diagnostic categories. One of the first steps in developing this personalized approach to treatment was the use of genetic markers to guide pharmacotherapeutics based on predictions of pharmacological response or non-response, and the potential risk of adverse drug reactions. Advances in technology have made a greater degree of specificity or precision potentially more attainable. To date, however, the search for precision has largely focused on biological parameters. Psychiatric disorders involve multi-level dynamics that require measures of phenomenological, psychological, behavioral, social structural, and cultural dimensions. This points to the need to develop more fine-grained analyses of experience, self-construal, illness narratives, interpersonal interactional dynamics, and social contexts and determinants of health. In this paper, we review the limitations of precision psychiatry arguing that it cannot reach its goal if it does not include core elements of the processes that give rise to psychopathological states, which include the agency and experience of the person. Drawing from contemporary systems biology, social epidemiology, developmental psychology, and cognitive science, we propose a cultural-ecosocial approach to integrating precision psychiatry with person-centered care.

PMID:36845417 | PMC:PMC9947537 | DOI:10.3389/fnins.2023.1041433

Front Genet. 2023 Feb 9;14:1143789. doi: 10.3389/fgene.2023.1143789. eCollection 2023.

NO ABSTRACT

PMID:36845385 | PMC:PMC9948396 | DOI:10.3389/fgene.2023.1143789

Int J Parasitol Parasites Wildl. 2023 Feb 9;20:138-152. doi: 10.1016/j.ijppaw.2023.02.002. eCollection 2023 Apr.

ABSTRACT

Sucking lice live in intimate association with their hosts and often display a high degree of host specificity. The present study investigated sucking lice of the genus Lemurpediculus from six mouse lemur (Microcebus) and two dwarf lemur (Cheirogaleus) species endemic to the island of Madagascar, considered a biodiversity hotspot. Louse phylogenetic trees were created based on cytochrome C oxidase subunit I (COI), elongation factor 1α (EF1α) and internal transcribed spacer 1 (ITS1) sequences. While clustering according to host species was generally observed for COI and ITS1, suggesting high host specificity of the examined lice, EF1α sequences alone did not distinguish between lice of different Microcebus species, possibly due to rather recent divergence. As bootstrap support for basal tree structure was rather low, further data are necessary to resolve the evolutionary history of louse-mouse lemur associations. Three new species of sucking lice are described: Lemurpediculus zimmermanni sp. Nov. From Microcebus ravelobensis, Lemurpediculus gerpi sp.nov. from Microcebus gerpi, and Lemurpediculus tsimanampesotsae sp. nov. from Microcebus griseorufus. These new species are compared with all known congeneric species and identifying features are illustrated for all known species of Lemurpediculus.

PMID:36845223 | PMC:PMC9945782 | DOI:10.1016/j.ijppaw.2023.02.002

Front Immunol. 2023 Feb 9;14:1117320. doi: 10.3389/fimmu.2023.1117320. eCollection 2023.

ABSTRACT

The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56bright NK cells in regulating tissue homeostasis remains incompletely understood. A targeted single-cell mRNA analysis revealed distinct transcriptional differences between matched human peripheral blood and intrahepatic CD56bright NK cells. Multiparameter flow cytometry identified a cluster of intrahepatic NK cells with overlapping high expression of CD56, CD69, CXCR6, TIGIT and CD96. Intrahepatic CD56bright NK cells also expressed significantly higher protein surface levels of TIGIT, and significantly lower levels of DNAM-1 compared to matched peripheral blood CD56bright NK cells. TIGIT+ CD56bright NK cells showed diminished degranulation and TNF-α production following stimulation. Co-incubation of peripheral blood CD56bright NK cells with human hepatoma cells or primary human hepatocyte organoids resulted in migration of NK cells into hepatocyte organoids and upregulation of TIGIT and downregulation of DNAM-1 expression, in line with the phenotype of intrahepatic CD56bright NK cells. Intrahepatic CD56bright NK cells represent a transcriptionally, phenotypically, and functionally distinct population of NK cells that expresses higher levels of TIGIT and lower levels of DNAM-1 than matched peripheral blood CD56bright NK cells. Increased expression of inhibitory receptors by NK cells within the liver environment can contribute to tissue homeostasis and reduction of liver inflammation.

PMID:36845105 | PMC:PMC9948018 | DOI:10.3389/fimmu.2023.1117320

Microsyst Nanoeng. 2023 Feb 21;9:17. doi: 10.1038/s41378-023-00485-4. eCollection 2023.

ABSTRACT

Caenorhabditis elegans embryos have been widely used to study cellular processes and developmental regulation at early stages. However, most existing microfluidic devices focus on the studies of larval or adult worms rather than embryos. To accurately study the real-time dynamics of embryonic development under different conditions, many technical barriers must be overcome; these can include single-embryo sorting and immobilization, precise control of the experimental environment, and long-term live imaging of embryos. This paper reports a spiral microfluidic device for effective sorting, trapping, and long-term live imaging of single C. elegans embryos under precisely controlled experimental conditions. The device successfully sorts embryos from a mixed population of C. elegans at different developmental stages via Dean vortices generated inside a spiral microchannel and traps the sorted embryos at single-cell resolution through hydrodynamic traps on the sidewall of the spiral channel for long-term imaging. Through the well-controlled microenvironment inside the microfluidic device, the response of the trapped C. elegans embryos to mechanical and chemical stimulation can be quantitatively measured. The experimental results show that a gentle hydrodynamic force would induce faster growth of embryos, and embryos developmentally arrested in the high-salinity solution could be rescued by the M9 buffer. The microfluidic device provides new avenues for easy, rapid, high-content screening of C. elegans embryos.

PMID:36844938 | PMC:PMC9943735 | DOI:10.1038/s41378-023-00485-4

Front Artif Intell. 2023 Feb 9;6:1056422. doi: 10.3389/frai.2023.1056422. eCollection 2023.

ABSTRACT

In recent years, several deep learning approaches have been successfully applied in the field of medical image analysis. More specifically, different deep neural network architectures have been proposed and assessed for the detection of various pathologies based on chest X-ray images. While the performed assessments have shown very promising results, most of them consist in training and evaluating the performance of the proposed approaches on a single data set. However, the generalization of such models is quite limited in a cross-domain setting, since a significant performance degradation can be observed when these models are evaluated on data sets stemming from different medical centers or recorded under different protocols. The performance degradation is mostly caused by the domain shift between the training set and the evaluation set. To alleviate this problem, different unsupervised domain adaptation approaches are proposed and evaluated in the current work, for the detection of cardiomegaly based on chest X-ray images, in a cross-domain setting. The proposed approaches generate domain invariant feature representations by adapting the parameters of a model optimized on a large set of labeled samples, to a set of unlabeled images stemming from a different data set. The performed evaluation points to the effectiveness of the proposed approaches, since the adapted models outperform optimized models which are directly applied to the evaluation sets without any form of domain adaptation.

PMID:36844424 | PMC:PMC9948081 | DOI:10.3389/frai.2023.1056422

Front Plant Sci. 2023 Feb 9;14:1102181. doi: 10.3389/fpls.2023.1102181. eCollection 2023.

ABSTRACT

Peanut is an important oil and food legume crop grown in more than one hundred countries, but the yield and quality are often impaired by different pathogens and diseases, especially aflatoxins jeopardizing human health and causing global concerns. For better management of aflatoxin contamination, we report the cloning and characterization of a novel A. flavus inducible promoter of the O-methyltransferase gene (AhOMT1) from peanut. The AhOMT1 gene was identified as the highest inducible gene by A. flavus infection through genome-wide microarray analysis and verified by qRT-PCR analysis. AhOMT1 gene was studied in detail, and its promoter, fussed with the GUS gene, was introduced into Arabidopsis to generate homozygous transgenic lines. Expression of GUS gene was studied in transgenic plants under the infection of A. flavus. The analysis of AhOMT1 gene characterized by in silico assay, RNAseq, and qRT-PCR revealed minute expression in different organs and tissues with trace or no response to low temperature, drought, hormones, Ca2+, and bacterial stresses, but highly induced by A. flavus infection. It contains four exons encoding 297 aa predicted to transfer the methyl group of S-adenosyl-L-methionine (SAM). The promoter contains different cis-elements responsible for its expression characteristics. Functional characterization of AhOMT1P in transgenic Arabidopsis plants demonstrated highly inducible behavior only under A. flavus infection. The transgenic plants did not show GUS expression in any tissue(s) without inoculation of A. flavus spores. However, GUS activity increased significantly after inoculation of A. flavus and maintained a high level of expression after 48 hours of infection. These results provided a novel way for future management of peanut aflatoxins contamination through driving resistance genes in A. flavus inducible manner.

PMID:36844094 | PMC:PMC9947529 | DOI:10.3389/fpls.2023.1102181

Front Plant Sci. 2023 Feb 10;14:1129738. doi: 10.3389/fpls.2023.1129738. eCollection 2023.

NO ABSTRACT

PMID:36844083 | PMC:PMC9950732 | DOI:10.3389/fpls.2023.1129738

iScience. 2023 Feb 3;26(3):106118. doi: 10.1016/j.isci.2023.106118. eCollection 2023 Mar 17.

ABSTRACT

Different evolutionary processes push cancers to increasingly aggressive behaviors, energetically sustained by metabolic reprogramming. The collective signature emerging from this transition is macroscopically displayed by positron emission tomography (PET). In fact, the most readily PET measure, the maximum standardized uptake value (SUVmax), has been found to have prognostic value in different cancers. However, few works have linked the properties of this metabolic hotspot to cancer evolutionary dynamics. Here, by analyzing diagnostic PET images from 512 patients with cancer, we found that SUVmax scales superlinearly with the mean metabolic activity (SUVmean), reflecting a dynamic preferential accumulation of activity on the hotspot. Additionally, SUVmax increased with metabolic tumor volume (MTV) following a power law. The behavior from the patients data was accurately captured by a mechanistic evolutionary dynamics model of tumor growth accounting for phenotypic transitions. This suggests that non-genetic changes may suffice to fuel the observed sustained increases in tumor metabolic activity.

PMID:36843844 | PMC:PMC9950952 | DOI:10.1016/j.isci.2023.106118

Mater Horiz. 2023 Feb 27. doi: 10.1039/d2mh01267g. Online ahead of print.

ABSTRACT

Polymerase chain reaction (PCR)-based diagnostic kits for point-of-care (POC) testing are highly desirable to prevent the spread of infectious diseases. Here, we demonstrate a rapid PCR testing kit that involves integrating a lateral flow paper strip with a nichrome-based thin film heater. The use of a paper membrane as a PCR-solution container results in fast thermocycling without a cooler because the membrane can contain the solution with a high specific surface area where Joule heating is applied. After PCR, amplified products are simultaneously detected at the lateral flow paper strip with the naked eye. Severe acute respiratory syndrome β-coronavirus RNA can be detected within 30 min after PCR solution injection. This work reveals that the paper membrane can act as not only a capillary flow channel but also as a promising platform for fast PCR and detection.

PMID:36843375 | DOI:10.1039/d2mh01267g

Crit Rev Biotechnol. 2023 Feb 26:1-15. doi: 10.1080/07388551.2023.2166455. Online ahead of print.

ABSTRACT

Carbon neutrality by 2050 has become one of the most urgent challenges the world faces today. To address the issue, it is necessary to develop and promote new technologies related with CO2 recycling. Cyanobacteria are the only prokaryotes performing oxygenic photosynthesis, capable of fixing CO2 into biomass under sunlight and serving as one of the most important primary producers on earth. Notably, recent progress on synthetic biology has led to utilizing model cyanobacteria such as Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 as chassis for "light-driven autotrophic cell factories" to produce several dozens of biofuels and various fine chemicals directly from CO2. However, due to the slow growth rate and low biomass accumulation in the current chassis, the productivity for most products is still lower than the threshold necessary for large-scale commercial application, raising the importance of developing high-efficiency cyanobacterial chassis with fast growth and/or higher biomass accumulation capabilities. In this article, we critically reviewed recent progresses on identification, systems biology analysis, and engineering of fast-growing cyanobacterial chassis. Specifically, fast-growing cyanobacteria identified in recent years, such as S. elongatus UTEX 2973, S. elongatus PCC 11801, S. elongatus PCC 11802 and Synechococcus sp. PCC 11901 was comparatively analyzed. In addition, the progresses on their recent application in converting CO2 into chemicals, and genetic toolboxes developed for these new cyanobacterial chassis were discussed. Finally, the article provides insights into future challenges and perspectives on the synthetic biology application of cyanobacterial chassis.

PMID:36842999 | DOI:10.1080/07388551.2023.2166455

Trends Genet. 2023 Feb 24:S0168-9525(23)00022-7. doi: 10.1016/j.tig.2023.01.007. Online ahead of print.

ABSTRACT

Clonal selection and drift drive both normal tissue and cancer development. However, the biological mechanisms and environmental conditions underpinning these processes remain to be elucidated. Clonal selection models are centered in Darwinian evolutionary theory, where some clones with the fittest features are selected and populate the tissue or tumor. We suggest that different subclasses of stem cells, each of which is responsible for a distinct feature of the selection process, share common features between normal and cancer conditions. While active stem cells populate the tissue, dormant cells account for tissue replenishment/regeneration in both normal and cancerous tissues. We also discuss potential mechanisms that drive clonal drift, their interactions with clonal selection, and their similarities during normal and cancer tissue development.

PMID:36842901 | DOI:10.1016/j.tig.2023.01.007

Cytokine. 2023 Feb 24;164:156164. doi: 10.1016/j.cyto.2023.156164. Online ahead of print.

ABSTRACT

Various studies have investigated the risk of preeclampsia with the forkhead box protein P3 (FOXP3) gene rs2232365 and rs3761548 polymorphisms. However, the results remained contradictory. A comprehensive literature search was conducted using the Cochrane Library, PubMed, and Web of Science (up to Oct 11, 2021). Meta-analysis was carried out in the R language environment for statistical computing and graphics. A fixed-effect or random-effects model was used according to the statistical significance of heterogeneity among included studies. The pooled odds ratios and corresponding 95% confidence intervals were calculated to estimate the strength of the effect. For the rs2232365 polymorphism, statistical significance was detected neither in the overall population nor among the East Asian and West Asian subgroups. However, for rs3761548, the summarized statistics revealed a significant association between the C allele carriage and preeclampsia risk in the homozygote, heterozygote, and dominant models. The further stratified analysis found this effect might be specific to West-South Asian ethnic subgroups. To sum up, this meta-analysis showed that the FOXP3 rs3761548 polymorphism was significantly associated with preeclampsia susceptibility, and it had a deleterious effect especially in the West-South Asian population. In contrast, rs2232365 may serve as neither a protective nor a risk factor for preeclampsia onset.

PMID:36842371 | DOI:10.1016/j.cyto.2023.156164

Prostate. 2023 Feb 26. doi: 10.1002/pros.24500. Online ahead of print.

ABSTRACT

BACKGROUND: New evidence suggests that bacteria-produced DNA toxins may have a role in the development or progression of prostate cancer. To determine the prevalence of these genes in a noninfection (i.e., colonized) state, we screened urine specimens in men before undergoing a biopsy for prostate cancer detection.

METHODS: We developed a multiplex polymerase chain reaction using three of the most described bacterial genotoxin gene primers: Colibactin (polyketone synthase [pks] gene island: clbN and clbB), cytotoxic necrotizing factor (cnf1) toxin, and cytolethal distending toxin B (cdtB) represented gene islands. After calibration on Escherichia coli samples of known genotypes, we used a training and validation cohort. We performed multiplex testing on a training cohort of previously collected urine from 45 men undergoing prostate biopsy. For the validation cohort, we utilized baseline urine samples from a previous randomized clinical trial (n = 263) with known prostate cancer outcomes.

RESULTS: The prevalence of four common bacterial genotoxin genes detected in the urine before prostate biopsy for prostate cancer is 8% (25/311). The prevalence of pks island (clbN and clbB), cnf1, and cdt toxin genes are 6.1%, 2.4%, and 1.7%, respectively. We found no association between urinary genotoxins and prostate cancer (p = 0.83). We did identify a higher proportion of low-grade cancer (92% vs. 44%) in those men positive for urinary genotoxin and higher-grade cancer in those genotoxin negative (8% vs. 56%, p = 0.001).

CONCLUSIONS: The prevalence of urinary genotoxins is low and does not correspond to a prostate cancer diagnosis. The urine was taken at one point in time and does not rule out the possibility of previous exposure.

PMID:36842100 | DOI:10.1002/pros.24500

J Mol Cell Cardiol. 2023 Feb 23;177:28-37. doi: 10.1016/j.yjmcc.2023.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have implicated p53-dependent mitochondrial dysfunction in sepsis induced end organ injury, including sepsis-induced myocardial dysfunction (SIMD). However, the mechanisms behind p53 localization to the mitochondria have not been well established. Dynamin-related protein 1 (Drp1), a mediator of mitochondrial fission, may play a role in p53 mitochondrial localization. Here we examined the role of Drp1/p53 interaction in SIMD using in vitro and murine models of sepsis.

METHODS: H9c2 cardiomyoblasts and BALB/c mice were exposed to lipopolysaccharide (LPS) to model sepsis phenotype. Pharmacologic inhibitors of Drp1 activation (ψDrp1) and of p53 mitochondrial binding (pifithrin μ, PFTμ) were utilized to assess interaction between Drp1 and p53, and the subsequent downstream impact on mitochondrial morphology and function, cardiomyocyte function, and sepsis phenotype.

RESULTS: Both in vitro and murine models demonstrated an increase in physical Drp1/p53 interaction following LPS treatment, which was associated with increased p53 mitochondrial localization, and mitochondrial dysfunction. This Drp1/p53 interaction was inhibited by ΨDrp1, suggesting that this interaction is dependent on Drp1 activation. Treatment of H9c2 cells with either ΨDrp1 or PFTμ inhibited the LPS mediated localization of Drp1/p53 to the mitochondria, decreased oxidative stress, improved cellular respiration and ATP production. Similarly, treatment of BALB/c mice with either ΨDrp1 or PFTμ decreased LPS-mediated mitochondrial localization of p53, mitochondrial ROS in cardiac tissue, and subsequently improved cardiomyocyte contractile function and survival.

CONCLUSION: Drp1/p53 interaction and mitochondrial localization is a key prodrome to mitochondrial damage in SIMD and inhibiting this interaction may serve as a therapeutic target.

PMID:36841153 | DOI:10.1016/j.yjmcc.2023.01.008