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Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Mitochondrial membrane potential (MMP) and mitochondrial mass (MM) affect mitochondrial function and lymphocyte activation, but few studies on HBV infection exist. This study aimed to investigate the regulatory mechanism of mitochondrial dysfunction during HBV infection and its clinical significance by analyzing the alterations of MM and MMP in peripheral blood immune cells. The study enrolled 90 participants, including healthy volunteers(HC) and patients with HBV infection, HBV patients were divided into chronic hepatitis B patients (CHB) and liver cirrhosis (LC) according to the study, and CHB was also divided into an inflammation group and a non-inflammation group. Flow cytometry was used to analyze the changes of MM and MMP in peripheral blood immune cells. These analyses were correlated with the presence of CHB and LC and indexes related to liver inflammation. The study revealed significant variations in the percentage of MMP and MM of CD8 T cells associated with the progression of the disease. The MMP percentage of CD8 T cells in the LC group exhibited a notable decrease compared to the HC group and CHB groups. Moreover, MMP of CD8 T cells demonstrated potential in distinguishing CHB and LC (AUC=0.7341, P=0.0032). Furthermore, in exploring the link between mitochondrial function of immune cells and liver inflammation, the study found a negative correlation between the MMP ratio of CD4 T and CD8 T cells and AST (p=0.0039 and P=0.0070, r=-0.4405 and r=-0.4146), while the MM of CD8 T cells displayed a positive correlation with AST (p=0.0013, r=0.4865). In CHB patients with normal ALT but liver inflammation detected on B-scan ultrasonography, a significant decrease was observed in the MMP percentage of CD8 T (66.13 ± 14.27), CD56 NK(57.77 ± 17.40) and CD4 CD8 T (61.98 ± 15.98) cells. Furthermore, it was also found that the percentage of MMP in CD4 CD8 T cells could serve as an indicator for early liver inflammation and injury (AUC=0.8408, P=0.0052). In this study, we conducted a systematic analysis of the percentage of lymphocyte MMP and MM in various stages of HBV infection. Our findings revealed a correlation between MMP and MM and early liver inflammation, as well as the progression of the infection. This study marked the first demonstration of the clinical diagnostic value of MMP and MM in HBV infection. Furthermore, this was the first study to discuss the mitochondria of lymphocytes and liver inflammation in HBV infection. It enhanced the understanding of the role of T cells in liver inflammation, and elucidated potential markers for the early detection of liver injury and clinical cirrhosis.

To explore the difference of peripheral immune indexes especially T subsets cell mitochondrial indexes in patients with chronic HBV infection (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC) and healthy controls (HCs). From May 2023 to December 2023, HBV infected patients aged 40–59 years (HBV infection group, 236 cases) and healthy people of the same age group (control group, 112 cases) were selected as the study objects. More than 80 parameters related to lymphocyte including cell percentage, absolute count, mitochondrial mass and mitochondrial low membrane potential were obtained by flow cytometry. The mitochondrial mass of memory T cells was found to be sequentially raised in the disease progression of hepatitis B patients from CHB to LC and eventually to HCC, and mitochondrial low membrane potential ratio was sequentially decreased. Then we screened out 4 main indicators related to the stage of disease progression in HBV-infected patients and distinguished the differences among the control group, CHB, LC, and HCC groups through the calculation of MPOLS (mitochondrial parameters of lymphocyte subsets) value, which can be used as a novel biomarker for hepatitis B disease progression. Mitochondrial parameters of peripheral lymphocytes in HBV-infected patients are significant indicators of different stages of disease progression. The MPOLS provides rich clinical data support for clinical early warning of high-risk hepatitis B patients, and we believe that the MPOLS can be combined with a variety of clinical characteristics to achieve more accurate diagnosis and treatment.

To characterise T‐cell immunity and inflammatory profiles in HIV patients with mycobacterial co‐infections. This study enrolled 41 HIV patients co‐infected with Mycobacterium tuberculosis (HIV‐TB, n = 27) or non‐tuberculous mycobacteria (HIV‐NTM, n = 14), along with 30 controls (20 HIV‐monoinfected, 10 post‐treatment) from a single centre. Flow cytometry quantified T‐cell subsets (CD3 + CD4+, CD3 + CD8+, CD28+ subsets), mitochondrial parameters (mass [MM], low membrane potential [MMP‐low%]) and cytokines (IFN‐γ, IL‐2/4/6/10/17A, TNF‐α). Co‐infected groups showed reduced T‐cell counts versus HIV‐monoinfected controls (p < 0.05). Elevated MMP‐low% in CD3 + CD4+/CD28+ T cells indicated mitochondrial dysfunction in co‐infected patients (p < 0.05). HIV‐TB patients exhibited higher CD3 + CD4+/CD28+/CD8+ T‐cell MM than HIV‐NTM (p < 0.05), while HIV‐NTM demonstrated greater MMP‐low% (p < 0.05). Proinflammatory cytokines (IFN‐γ, IL‐6, IL‐17A) inversely correlated with CD4+ counts and MM, but positively with CD8 + CD28+ MMP‐low%. MMP‐low% in CD3 + CD4 + CD28+ T cells and IL‐2 differentiated IRIS/non‐IRIS cases (p < 0.05), with combined AUC = 0.834 for IRIS prediction (p = 0.001). HIV/mycobacterial co‐infection exacerbates T‐cell depletion and mitochondrial dysfunction, with HIV‐NTM showing more severe impairment. MMP‐low% and IL‐2 may serve as biomarkers for IRIS risk stratification.

Biological effects of high fluence low-power (HFLP) lasers have been reported for some time, yet the molecular mechanisms procuring cellular responses remain obscure. A better understanding of the effects of HFLP lasers on living cells will be instrumental for the development of new experimental and therapeutic strategies. Therefore, we investigated sub-cellular mechanisms involved in the laser interaction with human hepatic cell lines. We show that mitochondria serve as sub-cellular “sensor” and “effector” of laser light non-specific interactions with cells. We demonstrated that despite blue and red laser irradiation results in similar apoptotic death, cellular signaling and kinetic of biochemical responses are distinct. Based on our data, we concluded that blue laser irradiation inhibited cytochrome c oxidase activity in electron transport chain of mitochondria. Contrary, red laser triggered cytochrome c oxidase excessive activation. Moreover, we showed that Bcl-2 protein inhibited laser-induced toxicity by stabilizing mitochondria membrane potential. Thus, cells that either overexpress or have elevated levels of Bcl-2 are protected from laser-induced cytotoxicity. Our findings reveal the mechanism how HFLP laser irradiation interfere with cell homeostasis and underscore that such laser irradiation permits remote control of mitochondrial function in the absence of chemical or biological agents.

Mitochondrial diseases impair oxidative phosphorylation and ATP production, while effective treatment is still lacking. Defective complex III is associated with a highly variable clinical spectrum. We show that pyocyanin, a bacterial redox cycler, can replace the redox functions of complex III, acting as an electron shunt. Sub-μM pyocyanin was harmless, restored respiration and increased ATP production in fibroblasts from five patients harboring pathogenic mutations in TTC19 , BCS1L or LYRM7 , involved in assembly/stabilization of complex III. Pyocyanin normalized the mitochondrial membrane potential, and mildly increased ROS production and biogenesis. These in vitro effects were confirmed in both Drosophila TTC19KO and in Danio rerio TTC19KD , as administration of low concentrations of pyocyanin significantly ameliorated movement proficiency. Importantly, daily administration of pyocyanin for two months was not toxic in control mice. Our results point to utilization of redox cyclers for therapy of complex III disorders. Mitochondrial diseases, including those caused by defects in complex III of the respiratory chain, lack curative treatments. Here the authors report that the small molecule pyocyanin has beneficial effects in cells derived from patients with complex III-deficiency as well as in fly and zebrafish genetic models with reduced complex III activity.

Background Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue–like injured brain.

As a cardiovascular disease, coronary heart disease (CHD) is characterized by poor prognosis and increasing morbidity and mortality rates. Echinacoside (ECH) can protect against multiple cardiovascular diseases due to its antioxidant and anti-inflammatory properties. However, the role of ECH in CHD remains unclear. In ECH-treated human coronary artery endothelial cells (HCAECs), cell viability, NO production, endothelial nitric oxide synthase (eNOS) expression, and angiogenesis ability were detected using cell counting kit-8 (CCK-8) assay, diaminofluorescein-FM diacetate (DAF-FM DA) staining, western blot, and tube formation assay, respectively. The activities of oxidative stress markers were detected using dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay and corresponding assay kits. Cell apoptosis was detected utilizing flow cytometry and caspase3 assay. Western blot was used to detect the expressions of Nrf2/PPARγ signaling pathway- and mitochondrial dynamics-related proteins. Mitochondrial membrane potential and mitochondrial fusion and fission were detected using JC-1 staining and immunofluorescence (IF) assay. In this study, ECH was found to revive the viability, ameliorate the endothelial dysfunction, suppress oxidative stress, and inhibit the apoptosis in ox-LDL-induced HCAECs via activating Nrf2/PPARγ signaling pathway, which were all abolished following the treatment of Nrf2 inhibitor ML385. It was also identified that ECH regulated mitochondrial fusion-fission balance in ox-LDL-induced HCAECs through the activation of Nrf2/PPARγ signaling pathway. In summary, ECH activated Nrf2/PPARγ signaling pathway to regulate mitochondrial fusion-fission balance, thereby improving ox-LDL-induced dysfunction of HCAECs.

Neuronal excitation imposes a high demand of ATP in neurons. Most of the ATP derives primarily from pyruvate-mediated oxidative phosphorylation, a process that relies on import of pyruvate into mitochondria occuring exclusively via the mitochondrial pyruvate carrier (MPC). To investigate whether deficient oxidative phosphorylation impacts neuron excitability, we generated a mouse strain carrying a conditional deletion of MPC1, an essential subunit of the MPC, specifically in adult glutamatergic neurons. We found that, despite decreased levels of oxidative phosphorylation and decreased mitochondrial membrane potential in these excitatory neurons, mice were normal at rest. Surprisingly, in response to mild inhibition of GABA mediated synaptic activity, they rapidly developed severe seizures and died, whereas under similar conditions the behavior of control mice remained unchanged. We report that neurons with a deficient MPC were intrinsically hyperexcitable as a consequence of impaired calcium homeostasis, which reduced M-type potassium channel activity. Provision of ketone bodies restored energy status, calcium homeostasis and M-channel activity and attenuated seizures in animals fed a ketogenic diet. Our results provide an explanation for the seizures that frequently accompany a large number of neuropathologies, including cerebral ischemia and diverse mitochondriopathies, in which neurons experience an energy deficit.