mitochondria

43-year-old lady presented with incidentally discovered liver lesions while she was being managed for her complaints of menorrhagia. CT and MRI showed hepatomegaly with multiple lesions in both lobes of the liver with vascular element in the background of diffuse fatty infiltration. Patient underwent laparoscopic core biopsy. Histopathology showed extensive steatosis, intracytoplasmic giant mitochondria and absence of portal tracts, features highly suggestive of hepatic adenomatosis. IHC staining showed membranous and cytoplasmic positivity in hepatocytes for B-catenin consistent with multiple hepatic adenomatosis. Hepatic adenomatosis is a new clinical entity in the hepatological practice characterized by the presence of 10 or more nodules in the liver known for its major complication of bleeding. Hepatic adenomatosis is managed by regular imaging and resection of large (> 5cm) superficial and painful adenomas along with liver function tests and tumor markers to rule out malignant transformation. However, the potential cure being the liver transplantation.

Owing to the ever westernizing lifestyles in developing countries like India, the escalation of oral cancer patients are in need of urgent plan of action. With tobacco being the commonest cause for causation of oral cancer, Global Adult Tobacco Survey, 2016-17 revealed that almost 28% of whole population of India is consuming tobacco in either smoking or smokeless form. With these increasing numbers, the expected death toll to be expected to touch 1-2 million mark by the year 2035 [1]. Although, the current Onco-medicine fraternity excels in rendering care to oral cancer patients in the form of surgeries, chemotherapy and radiation-therapy. Often, these treatment modalities impart some unwanted adverse effects like, docetaxel (DCT) is known for its hepatotoxicity [2,3] whereas, one of the commonly used cisplatin (CIS) presents with nephrotoxicity, neurotoxicity, bone marrow suppression and vomiting [4,5]. Literature suggests of many non conventional medicaments being tested in past for their anti onco-genic effect, where few being effective and others being questionable ones. Chlorhexidine being one among them showing some how promising anti onco-genic activity with feeble amount of studies being conducted in past. Chlorhexidine, one of the most commonly prescribed mouthrinse in the field of dentistry, with varying concentrations of 0.12% and 0.2% concentrations. Although, apart from being broad spectrum antibiotic, its capability to dismantle the protein – protein bond between anti – apoptotic Bcl-2 family protein Bcl-xL and its pro – apoptotic binding partners [6]. The current study was conducted on three cell lines of squamous cell carcinoma (SCC-4, SCC-9, SCC -15) and two pharynx carcinoma cell lines (FaDu and Detroit 562). The compounds induced apoptosis through mitochondria dependent apoptotic pathway in oral tumour cell lines. Another study conducted to assess the similar anti – oncogenic activites of chlorhexidine mouthrinse along with cranberry [7]. It was evident from results that, with increasing concentrations of chlorhexidine mouthrinse, there was increase in mean percent growth inhibition. The authors concluded saying, chlorhexidine has showed both anti cancerous as well as anti bacterial activity required to tackle common oral infections, part of common anti cancer therapy. Fernando Martínez-Pérez et al (2019) conducted study, where antitumor activity of Lipophilic Bismuth Nanoparticles (BisBAL NPs) and chlorhexidine on human squamous cell carcinoma was assessed using energy dispersive X – ray spectroscopy in conjunction with scanning electron microscopy (EDS-SEM). Study revealed, BisBAL NPs and chlorhexidine both showed cell growth inhibition on both cancer cell line (CAL-27) and human gingival fibroblasts (HGFs). Although, chlorhexidine showed non specific cytotoxicity for both tumoral and non tumoral control cells. The suggestive mechanism of action might be loss of cell membrane integrity [8]. Although Eliot MN (2013) conducted study, to assess the risk of head and neck squamous cell carcinoma secondary to use of alcohol containing and non alcoholic mouthwashes including chlorhexidine. The study was concluded with an assumption based on chlorhexidine mouthwash alters the oral flora [9], thus resulting in increasing risk exponentially through diverse change in oral bacteria and altered immune response with contribution towards genesis or promotion of cancer [10]. On the contrary, alcohol consumption and smoking are predisposing factors towards upper digestive tract cancer. The main causative factor being the first metabolite of alcohol, acetaldehyde. And much higher levels are derived from oral bacteria and thus, same can be altered in favour through usage of chlorhexidine mouthwash, to avoid excessive production of acetaldehyde intra orally. In conclusion, chlorhexidine mouthwash has been into dental practice since long and the role it plays in either ways has to be assessed by a multi dimensional study with cell lines including that of control to derive better compared conclusions.

tRNA-dependent amidotransferases (AdT) are essential enzymes for protein biosynthesis in many bacteria and in all archaea. As AdT is essential for a number of pathogenic bacteria, and it is absent from mammalian cytoplasm, it is considered as a putative target for novel inhibitors that could be lead compounds to develop a new class of antibiotics. Besides GatFAB of Saccharomyces cerevisiae mitochondria and GatAB of Plasmodium falciparum apicoplast, all reported AdT can be divided into two groups: heterodimeric GatDE and heterotrimeric GatCAB. The latter is required to catalyze the conversion of Glu-tRNAGln and/or Asp-tRNAAsn into Gln-tRNAGln and/or Asn-tRNAAsn in many pathogenic bacteria. Recently determined high resolution crystal structures of several GatCAB could be used to design new inhibitors. In this review, we highlight the essential role of AdT for the faithful translation of glutamine and/or asparagine codons, we describe important features of the crystal structures of several GatCAB as well as tRNA/AdT/aaRS complexes for the formation of Gln-tRNAAsn and Asn-tRNAAsn, we finally summarize discoveries of AdT inhibitors based on their analogy to glutamine, adesosine tripoliphosphate and 3’-end of tRNA.

Understanding the obesity-related genes may provide future therapeutic strategies to modulate disease progression. UCP2 separates oxidative phosphorylation (OXPHOS) from ATP production in the inner mitochondria. Figure 1 shows the differences among UCP1, 2, 3. The main role of UCP2 is controlling the metabolism of energy in the cells [1-3]. Besides that, the expression of UCP2 is associated with chronic inflammation due to reactive oxygen species (ROS). In this regard, in injured cells and tissues, ROS could be decreased by reducing the proton motor force by the anti-inflammatory effect of UCP2 [4].

The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed. 

Mitochondrial and lysosomal dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) leading to deficient energy production and defects in phagocytosis in endosomal-lysosomal pathway respectively. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of inheritance that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. In this review article, we summarized the spectrum of mtDNA depletion disorders along with minor learning of lysosomal storage diseases. This current article offers a perspective on the role of genetics in medical practice and how this role may evolve over the next several years.

As a vital index of the mitochondrial micro-environment, mitochondrial micro-viscosity plays a fundamental role in cell life activities. Normal mitochondrial viscosity is a necessary condition for the maintenance of normal life activities of mitochondria. Abnormal mitochondrial viscosity can lead to a series of mitochondria-related diseases. Therefore, it is essential to observe mitochondrial viscosity for physiological and pathological processes. Given the conventional viscosity measurement methods (viscometer, etc.) cannot monitor the changes in mitochondrial viscosity, the fluorescence method supplemented with the fluorescent probe is widely used to observe the changes in mitochondrial viscosity. In view of the booming development in this area, this review describes the applications of viscosity-responsive mitochondrial fluorescent probes in biological samples from the cellular and tissue levels. We hope that this review will deepen our understanding of mitochondrial viscosity and related fields, and promote the development of viscosity-sensitive mitochondrial probes and other organelle fluorescence probes.

Neurological disorders are a significant cause of mortality and disability across the world. The current aging population and population expansion have seen an increase in the prevalence of neurological and psychiatric disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis and schizophrenia. These pose a significant societal burden, especially in low - and middle-income countries. Many neurological disorders have complex mechanisms and lack definitive cures; thus, improving our understanding of them is essential. The pathophysiology of neurological disorders often includes inflammation, mitochondrial dysfunction and oxidative stress. Oxidative stress processes, especially the generation of reactive oxygen species, are key mechanisms in the development of neurological disorders. Oxidative stress refers to an imbalance between the production of reactive oxygen species and antioxidants that can counteract them. Through their impacts on the pathophysiology of neurological disorders, nutrients with anti-inflammatory, neuroprotective and antioxidative properties have been suggested to prevent or mitigate these disorders. Certain vitamins, minerals, polyphenols and flavonoids may have therapeutic effects as adjuvant treatments for neurological disorders. Diet quality is also a risk factor for some neurological and psychiatric disorders and addressing nutritional deficiencies may alleviate symptoms. Therefore, optimizing nutritional intake may represent a potential treatment or prevention strategy. This review summarizes a selection of promising nutrients for the prevention and amelioration of neurological disorders to provide a summary for scientists, clinicians and patients, which may improve understanding of the potential benefits of nutrients in the treatment of neurological disorders.

Meat species identification has become essential with the increasing events of frauds like the illegal slaughter of cows, meat adulteration, and substitution. Food scam directly influences public well-being, trade, and wildlife. In Pakistan, donkey meat is used as adulterants for cow meat and is considered Haram in Islamic concepts. In this study PCR, based detection methods are used for identification purposes. The mitochondrial gene cytochrome b has been used in this study to identify the origin of meat specie. Specie-specific primers of cyt b of cow and donkey were used for identification. DNA from different binary ratios of cow and donkey meat was extracted by the phenol-chloroform method. Ratios were made from 1-10 and extracted DNA was subjected to PCR to amplify the target fragment of the cyt b gene. Primers were sensitive to identifying species origin in all meat ratios. Multiplex PCR was designed to identify both species and the results were analyzed by gel electrophoresis. Fragment size of 309bp for cow and 475bp for donkey was observed.Results of the current study conclude that PCR assays, including multiplex PCR, is efficient and has a high sensitivity for even small amount of meat. It is concluded that multiplex PCR is useful and reliable for adulterated meat detection.

Acute myeloid leukaemia (AML) is the forefront disorder of the bone marrow among others that disrupt the normal production of blood cells and platelets. The bone marrow microenvironment or the bone marrow niche (BM niche) that orchestrates the proliferation and survival of Leukaemic stem cells (LSC) is the reason for relapse after complete remission and also chemotherapy drug resistance. As for most cancers oxidative phosphorylation, a fundamental mitochondrial process of energy production, is under focus for the treatment of AML and a novel strategy of targeting heat shock proteins appears as a promising route for further research.

Amyotrophic lateral sclerosis (ALS) disease is characterized by degeneration of motor neurons and elevation of brain oxidative stress. Previous studies demonstrated the neuroprotective effects of Telomerase reverse transcriptase (TERT) from oxidative stress. We showed that increasing TERT expression in the brain of the Tg hSOD1G93A mouse ALS model attenuated the disease pathology and increased the survival of motor neurons exposed to oxidative stress. How TERT increased the survival of motor neurons exposed to oxidative stress is not yet clear. Here we investigated the consequence of TERT depletion in motor neuron cells under normal and oxidative stress conditions and in mouse brains of TERT knockout mice, on the expression and activity of SOD1 and catalase enzymes. Depletion of mouse TERT caused mitochondrial dysfunction and impaired catalase and SOD1 activity. Compensation with hTERT restored the activity of SOD1. SOD1 expression increased in the brain of TERT KO and in ALS mice and decreased in the brain of WT mice treated with telomerase-increasing compounds. We suggest that the ability of TERT to protect neurons from oxidative stress affects the expression and activity of SOD1, in a TERT-dependent manner, and supports the notion of TERT as a therapeutic target for neurodegenerative diseases like ALS.

Sepsis, a life-threatening condition triggered by infection, poses a significant healthcare challenge with high mortality rates. The interplay between genetics and the immune response in sepsis, particularly in surgical and trauma patients, is complex and critical. Genetic polymorphisms, particularly in cytokine genes like TNF-α, IL-6, and IL-8, have been extensively studied for their influence on sepsis susceptibility, severity, and outcomes. Polymorphisms can alter gene expression and cytokine production, leading to variations in immune responses. Studies have also explored polymorphisms concerning sepsis in genes encoding CD86, TLR4, and SIRT6. This review highlights the association between genetic polymorphisms and inflammatory responses, focusing on their impact on sepsis outcomes in surgical and trauma patients. Genetic variations play a significant role in sepsis risk, severity, and prognosis, with potential implications for personalized therapeutic strategies. Biomarkers such as cytokine gene polymorphisms may aid in predicting sepsis risk and guiding treatment decisions. Complementary therapies like acupuncture and novel biomarkers like microvesicles carrying mitochondrial content provide additional avenues for personalized sepsis management. Furthermore, multiomics approaches offer promise in predicting postoperative outcomes in surgical patients. Understanding the genetic basis of sepsis is essential for improving prevention, diagnosis, and treatment, ultimately leading to better clinical outcomes. Combining genomics, bioinformatics, and clinical expertise, precision medicine can revolutionize sepsis management by tailoring interventions to individual genetic profiles, thus enhancing patient care and outcomes.

Ischemia-Reperfusion Injury (IRI) is the outcome of two intertwined pathological processes resulting from the shortage of blood flow to tissues and the subsequent restoration of circulation to a previously ischemic area. IRI (sometimes just one side of the dyad) remains one of the most challenging problems in several branches of emergency medicine. Mitochondrial and endoplasmic reticulum dysfunction is a crucial pathological factor involved in the development of IRI. The sigma-1 receptor (Sig1-R) is an intracellular chaperone molecule located between the mitochondria and endoplasmic reticulum with an apparent physiological role in regulating signaling between these cell organelles and serves as a safety mechanism against cellular stress. Therefore, amelioration of IRI is reasonably expected by the activation of the Sig1-R chaperone. Indeed, under cellular stress, Sig1-R agonists improve mitochondrial respiration and optimize endoplasmic reticulum function by sustaining high-energy phosphate synthesis. The discovery that N, N-dimethyltryptamine (DMT) is an endogenous agonist of the Sig1-R may shed light on yet undiscovered physiological mechanisms and therapeutic potentials of this controversial hallucinogenic compound. In this article, the authors briefly overview the function of Sig1-R in cellular bioenergetics with a focus on the processes involved in IRI and summarize the results of their in vitro and in vivo DMT studies aiming at mitigating IRI. The authors conclude that the effect of DMT may involve a universal role in cellular protective mechanisms suggesting therapeutic potentials against different components and types of IRIs emerging in local and generalized brain ischemia after stroke or cardiac arrest.

Mesoscopic modeling of complex systems involves thermodynamic nonequilibrium of discrete scaling. Further from quantum correlation on a chip retrieved quantum nonlinear optics with single photons enabled by strongly interacting atoms. Accompanied by mesofractals as the development of meso & micro size fractal structures is required to mimic various biological systems for various functions. Showed through fluorapatite in gelatin‐based nanocomposite, fractal in DNA knots driven by balance of fission & fusion in mtDNA/mitochondrial DNA mechanism, for optical engines for light energy detection described the proportional integral derivative [PI(D)]‐controller set in microbial cells to HCCI/Homogeneous Charge Compression Ignition.

Mitochondria are essential intracellular organelles that significantly influence various cellular processes, including metabolism, stress response, and cell fate. Their precise regulation is crucial for maintaining both organelle and cellular homeostasis. Wound healing is a complex, multifactorial process that relies on the coordinated actions of multiple cell types and numerous cellular mechanisms. Dysregulation in this process can lead to chronic wounds, which pose substantial challenges for healthcare systems and present limited treatment options due to their intricate pathogenesis. Recent research has increasingly focused on the role of mitochondria in wound healing, revealing their involvement in critical processes such as metabolism, apoptosis, and redox signaling. Mitochondrial dynamics play a vital role in wound healing by adapting to cellular demands and environmental cues. Moreover, mitophagy, the selective degradation of damaged mitochondria, is crucial for maintaining mitochondrial integrity and function during the healing process. Mitochondria are not only pivotal in energy production but also in calcium homeostasis and the generation of mitochondrial reactive oxygen species, which are essential for signaling during wound repair. As wound healing progresses through distinct yet overlapping stages mitochondria facilitate the energy demands of repair and contribute to cytoskeletal remodeling necessary for wound closure. Understanding the multifaceted roles of mitochondria in wound healing could lead to novel therapeutic approaches for chronic wounds. Future research should prioritize investigating mitochondrial dynamics and functions in human tissues to develop targeted strategies for enhancing wound healing outcomes.

The global menace of cancer requires supplementary treatments beyond standard medical approaches for effective medical intervention. The Ketogenic Diet (KD) composed of high fats combined with moderate proteins and low carbohydrates has become popular as a metabolic therapy for cancer. The anti-cancer mechanism of KD works through metabolic stress induction in cancer cells, reduced insulin and IGF-1 signaling pathways, improved mitochondrial function, inflammation, and immune regulation. Standard cancer treatments receive enhanced outcomes through KD synergistic action which simultaneously decreases treatment-related side effects. To achieve optimized treatment outcomes in cancer, ketogenic diet practitioners need to use personalized nutritional planning in combination with metabolic tracking and exogenous ketone supplements. It is essential to find solutions for diet adherence issues and nutrient deficiencies because they determine KD’s effectiveness as a cancer treatment. The fight against cancer needs sustained and multipronged clinical research and validation to establish the proper implementation of this method.

Background & objectives: Mitochondrial DNA (mtDNA) contains valuable genetic information and plays a crucial role in missing person investigations, mass disasters, and forensic cases involving limited or degraded biological material. mtDNA is maternally inherited, with a highly variable control region divided into three hypervariable regions are generally used for forensic investigation. This study aimed to evaluate maternal inheritance patterns of mtDNA using PCR-RFLP techniques to confirm maternal relatedness. Method: The study was designed after prior permission from the institute’s ethical committee in which subjects were enrolled. This pilot study analyzed 50 voluntary participants (mother-child pairs). DNA was extracted from blood or saliva, and the mtDNA hypervariable region (HV region) was amplified by PCR using specific primers for the HV1 region. The amplified fragments (1024 bp) were subjected to RFLP analysis using seven restriction endonucleases (Alu I, BsuR I (Hae III), Hinf I, HsYF31 (Dde I), Mbo I, Rsa I, and SsPI) to reveal morphotypes. Results: The study identified five morphotypes for Alu I, three for BsuR I (Hae III) and Rsa I, two for Hinf I, and one each for HsYF31 (Dde I), Mbo I, and SsPI. There was minimal genetic polymorphism in the hypervariable region among unrelated individuals, but consistent restriction patterns were observed between mothers and their children in same pair. Conclusion: The findings demonstrate the low genetic polymorphism in the hypervariable region among unrelated individuals and consistent restriction patterns within maternal pairs, underscoring mtDNA's utility in forensic and genealogical applications.