Exploring the pathogenetic mechanisms of Mycoplasmapneumoniae (Review).

Mycoplasmas, the smallest self-replicating prokaryotes without a cell wall, are the most prevalent and extensively studied species in humans. They significantly contribute to chronic respiratory tract illnesses and pneumonia, with children and adolescents being particularly vulnerable. Mycoplasma pneumoniae (M. pneumoniae) infections typically tend to be self-limiting and mild but can progress to severe or even life-threatening conditions in certain individuals. Extrapulmonary effects often occur without pneumonia, and both intrapulmonary and extrapulmonary complications operate through separate pathological mechanisms. The indirect immune-mediated damage of the immune system, vascular blockages brought on by vasculitis or thrombosis and direct harm from invasion or locally induced inflammatory cytokines are potential causes of extrapulmonary manifestations due to M. pneumoniae. Proteins associated with adhesion serve as the primary factor crucial for the pathogenicity of M. pneumoniae, relying on a specialized polarized terminal attachment organelle. The type and density of these host receptors significantly impact the adhesion and movement of M. pneumoniae, subsequently influencing the pathogenic mechanism and infection outcomes. Adjacent proteins are crucial for the proper assembly of the attachment organelle, with variations in the genetic domains of P1, P40 and P90 surfaces contributing to the variability of clinical symptoms and offering new avenues for developing vaccines against M. pneumoniae infections. M. pneumoniae causes oxidative stress within respiratory tract epithelial cells by adhering to host cells and releasing hydrogen peroxide and superoxide radicals. This oxidative stress enhances the vulnerability of host cells to harm induced by oxygen molecules. The lack of superoxide dismutase and catalase of bacteria allows it to hinder the catalase activity of the host cell, leading to the reduced breakdown of peroxides. Lung macrophages play a significant role in managing M. pneumoniae infection, identifying it via Toll-like receptor 2 and initiating the myeloid differentiation primary response gene 88-nuclear factor κΒ signaling cascade. However, the precise mechanisms enabling M. pneumoniae to evade intracellular host defenses remain unknown, necessitating further exploration of the pathways involved in intracellular survival. The present comprehensive review delves into the pathogenesis of M. pneumoniae infection within the pulmonary system and into extrapulmonary areas, outlining its impact.

Management of intracranial cavernous malformations using conservative vs. surgical and/or radiosurgical treatment: A systematic review and meta­analysis.

Intracranial cavernous malformations (CMs) are vascular lesions with a high bleeding rate. At present, the debate regarding their treatment is still ongoing. The present systematic review and meta-analysis aimed to evaluate the safety of surgery or radiosurgery (SRS) for the management of CMs and to determine their potential outcomes compared with conservative treatment. The present systematic review and meta-analysis investigated the relative articles involving the management of intracranial CMs, namely their natural history (conservative treatment) vs. surgical/SRS treatment through electronic databases until June, 2023. The collected variables included the first author's name, the study period covered, the year of publication, the total number of patients examined and their age, and the number of males. In total, six articles met the eligibility criteria. The total number of patients was 399 (157 in the surgery/SRS group and 242 in the conservative treatment group). The results revealed that surgical or SRS management is a safe procedure for CMs compared with conservative treatment. Notably, the use of hemosiderin in the pre-MRI, the free of seizures parameter and the neurological deficit parameters were associated with improved outcomes in the surgical or SRS group of patients.

Precision medicine for respiratory diseases: A current viewpoint.

In the realm of respiratory illnesses, despite the immense costs and efforts invested in diagnosis and treatment, numerous patients with chronic respiratory conditions or malignancies do not respond well to existing therapies. Delayed diagnoses and inadequate treatments contribute to these challenges, along with adverse reactions or treatment limitations due to side-effects. However, recent advancements in understanding respiratory diseases have paved the way for personalized medical treatments, considering individual genetic, molecular and environmental factors. Precision medicine, which accommodates individual differences in disease susceptibility and response to treatments, aims to improve patient care by aligning medical research with tailored therapies. Innovative technologies, such as genomic sequencing and biomarker identification contribute to this approach, allowing for customized treatments and the identification of effective therapies. Additionally, the application of precision medicine in lung cancer treatment exemplifies the forefront of individualized care within respiratory medicine. Several studies have explored the role of precision medicine in managing respiratory infectious diseases, asthma and idiopathic pulmonary fibrosis, aiming to categorize diseases more accurately and design targeted therapies. The ultimate goal is to enhance treatment effectiveness, minimize adverse events, and shift towards a patient-centered approach to managing respiratory conditions. Despite limitations, precision medicine holds promise for improving patient outcomes and emphasizing personalized care in respiratory medicine.

The parallel lives of pandemics: COVID­19 and obesity.

The present article discusses the interconnectedness of coronavirus disease 2019 (COVID-19) and obesity as global health crises. The similarities between the two conditions are highlighted; these include shared risk factors and comorbidities, and the impact of obesity on the immune system. The present article also mentions the challenges faced in combating both pandemics, including misinformation and prejudice against obesity. It discusses the development of therapeutic medications and vaccines for COVID-19 and the potential of injectable incretin analogues for weight loss. Socioeconomic issues are also addressed, with obesity being more prevalent in lower socioeconomic groups and the cost of obesity treatments being a barrier for those in need. The present article emphasizes the need for comprehensive and sustainable solutions, including public health interventions, education, policy changes and equitable distribution of resources, to address both COVID-19 and obesity.

Role of microRNAs in cognitive decline related to COVID­19 (Review).

The likelihood and severity of cognitive decline related to coronavirus disease 2019 (COVID-19) have been shown to be reflected by the severity of the infection and concomitant alterations in specific biomarkers. The present review discusses the role of microRNAs (miRNAs/miRs) as biomarkers in COVID-19 and the potential molecular mechanisms of cognitive dysfunction related to COVID-19. A systematic search of published articles was carried out from January 31, 2000 to December 31, 2022 using the PubMed, ProQuest, Science Direct and Google Scholar databases, combining the following terms: 'COVID-19' OR 'SARS-CoV-2' OR 'post-COVID-19 effects' OR 'cognitive decline' OR 'neurodegeneration' OR 'microRNAs'. The quality of the evidence was evaluated as high, moderate, low, or very low based on the GRADE rating. A total of 36 studies were identified which demonstrated reduced blood levels of miR-146a, miR-155, Let-7b, miR 31 and miR-21 in patients with COVID-19 in comparison with a healthy group. The overexpression of the Let-7b may result in the downregulation of BCL-2 during COVID-9 by adjusting the immune responses between chronic inflammatory disease, type 2 diabetes, COVID-19 and cognitive impairment. The reduced expression of miR-31 is associated with cognitive dysfunction and increased microcoagulability in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). miR-155 mediates synaptic dysfunction and the dysregulation of neurotransmitters due to acute inflammation, leading to brain atrophy and a subcortical cognitive profile. The downregulation of miR-21 in patients with COVID-19 aggravates systemic inflammation, mediating an uncontrollable immune response and the failure of T-cell function, provoking cognitive impairment in patients with SARS-CoV-2. On the whole, the present review indicates that dysregulated levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in the blood of individuals with COVID-19 are associated with cognitive decline, the chronic activation of immune mechanisms, the cytokine storm, and the vicious cycle of damage and systemic inflammation.

Genes encoding γ­glutamyl­transpeptidases in the allicin biosynthetic pathway in garlic (Allium sativum).

Allicin is a thiosulphate molecule produced in garlic (Allium sativum) and has a wide range of biological actions and pharmaceutical applications. Its precursor molecule is the non-proteinogenic amino acid alliin (S-allylcysteine sulphoxide). The alliin biosynthetic pathway in garlic involves a group of enzymes, members of which are the γ-glutamyl-transpeptidase isoenzymes, Allium sativum γ-glutamyl-transpeptidase AsGGT1, AsGGT2 and AsGGT3, which catalyze the removal of the γ-glutamyl group from γ-glutamyl-S-allyl-L-cysteine to produce S-allyl-L-cysteine. This removal is followed by an S-oxygenation, which leads to the biosynthesis of alliin. The aim of the present study is to annotate previously discovered genes of garlic γ-glutamyl-transpeptidases, as well as a fourth candidate gene (AsGGT4) that has yet not been described. The annotation includes identifying the loci of the genes in the garlic genome, revealing the overall structure and conserved regions of these genes, and elucidating the evolutionary history of these enzymes through their phylogenetic analysis. The genomic structure of γ-glutamyl-transpeptidase genes is conserved; each gene consists of seven exons, and these genes are located on different chromosomes. AsGGT3 and AsGGT4 enzymes contain a signal peptide. To that end, the AsGGT3 protein sequence was corrected; four indel events occurring in AsGGT3 coding regions suggested that at least in the garlic variety Ershuizao, AsGGT3 may be a pseudogene. Finally, the use of protein structure prediction tools allowed the visualization of the tertiary structure of the candidate peptide.

A mid­pandemic night's dream: Melatonin, from harbinger of anti­inflammation to mitochondrial savior in acute and long COVID­19 (Review).

Coronavirus disease 2019 (COVID­19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS­CoV­2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS­CoV­2 infection due to its good safety characteristics and broad­spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep­wake cycle and circadian rhythms. It exhibits oncostatic, anti­inflammatory, antioxidant and anti­aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID­19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well­established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID­19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID­19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.

Assessment of the effects of amphiphilic poly (N­vinylpyrrolidone) nanoparticles loaded with bortezomib on glioblastoma cell lines and zebrafish embryos.

Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (IC50 ~6.5 µg/ml) and in 3D multicellular tumor spheroids (IC50 ~8.5 µg/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.

Neurobiology of bruxism: The impact of stress (Review).

Bruxism is a non-functional involuntary muscle activity that affects more than one-third of the population at some point in their lives. A number of factors have been found to be related to the etiopathogenesis of bruxism; therefore, the condition is considered multifactorial. The most commonly accepted factor is stress. Stress has long been considered to increase muscle tone and to reduce the pain threshold. Current evidence indicates that exposure to chronic stress, distress and allostatic load ignite neurological degeneration and the attenuation of critical neuronal pathways that are highly implicated in the orofacial involuntary muscle activity. The present review discusses the negative effects that chronic stress exerts on certain parts of the central nervous system and the mechanisms through which these changes are involved in the etiopathogenesis of bruxism. The extent of these morphological and functional changes on nerves and neuronal tracts provides valuable insight into the obstacles that need to be overcome in order to achieve successful treatment. Additionally, particular emphasis is given on the effects of bruxism on the central nervous system, particularly the activation of the hypothalamic-pituitary-adrenal axis, as this subsequently induces an increase in circulating corticosterone levels, also evidenced by increased levels of salivary cortisol, thereby transforming bruxism into a self-reinforcing loop.

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review).

Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5­1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen­dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive­age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co­occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.

Role of decompressive craniectomy in the management of acute ischemic stroke (Review).

The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent.

Lung function at three months after hospitalization due to COVID­19 pneumonia: Comparison of alpha, delta and omicron variant predominance periods.

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant.

Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Temporal trends in laboratory parameters in survivors and non­survivors of critical COVID­19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

Risk factors for the in­hospital and 1­year mortality of elderly patients hospitalized due to COVID­19­related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high.

Role of vitamins beyond vitamin D3 in bone health and osteoporosis (Review).

The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and their potential roles in the development of osteoporosis. Epidemiological findings have demonstrated an association between vitamin deficiency and a higher risk of developing osteoporosis; vitamins are positively related to bone health upon their intake at the physiological range. Excessive vitamin intake can also adversely affect bone formation, as clearly demonstrated for vitamin A. Vitamins E (tocopherols and tocotrienols), K2 (menaquinones 4 and 7) and C have also been shown to promote osteoblast development through bone morphogenetic protein (BMP)/Smad and Wnt/ß­catenin signaling, as well as the TGFß/Smad pathway (α­tocopherol). Vitamin A metabolite (all­trans retinoic acid) exerts both inhibitory and stimulatory effects on BMP­ and Wnt/ß­catenin­mediated osteogenesis at the nanomolar and micromolar range, respectively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa­B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteoprotegerin (OPG), thus reducing the RANKL/OPG ratio and exerting anti­osteoclastogenic effects. Ascorbic acid can both promote and inhibit RANKL signaling, being essential for osteoclastogenesis. Vitamin K2 has also been shown to prevent vascular calcification by activating matrix Gla protein through its carboxylation. Therefore, the maintenance of a physiological intake of vitamins should be considered as a nutritional strategy for the prevention of osteoporosis.

Erratum: [Corrigendum] CD271+ stem cell treatment of patients with chronic stroke: A retrospective case series report.

[This corrects the article DOI: 10.3892/etm.2020.8948.].

Nutrient insufficiencies and deficiencies involved in the pathogenesis of bruxism (Review).

Stress has been well-documented to have a significant role in the etiopathogenesis of bruxism. Activation of the hypothalamic-pituitary-adrenal axis (HPA) and subsequent release of corticosteroids lead to increased muscle activity. Neurological studies have demonstrated that chronic stress exposure induces neurodegeneration of important neuronal structures and destabilization of the mesocortical dopaminergic pathway. These disruptions impair the abilities to counteract the overactivity of the HPA axis and disinhibit involuntary muscle activity, while at the same time, there is activation of the amygdala. Recent evidence shows that overactivation of the amygdala under stressful stimuli causes rhythmic jaw muscle activity by over activating the mesencephalic and motor trigeminal nuclei. The present review aimed to discuss the negative effects of certain vitamin and mineral deficiencies, such as vitamin D, magnesium, and omega-3 fatty acids, on the central nervous system. It provides evidence on how such insufficiencies may increase stress sensitivity and neuromuscular excitability and thereby reduce the ability to effectively respond to the overactivation of the sympathetic nervous system, and also how stress can in turn lead to these insufficiencies. Finally, the positive effects of individualized supplementation are discussed in the context of diminishing anxiety and oxidative stress, neuroprotection and in the reversal of neurodegeneration, and also in alleviating/reducing neuromuscular symptoms.

A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

[Corrigendum] Effect of the combination of Lactobacillus acidophilus (probiotic) with vitamin K3 and vitamin E on Escherichia coli and Staphylococcus aureus: An in vitro pathogen model and metastasis in vivo.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 3B on p. 7 showing the results of immunohistochemistry staining experiments, the data panels shown for the 'L+K' and 'EC+E+K' groups were strikingly similar, such that they appeared to be derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that Fig. 3B was inadvertently assembled incorrectly; specifically, the data shown for the 'L+K' group in Fig. 3B were featured incorrectly. The revised version of Fig. 3, now containing the correct data for the 'L+K' experimental group in Fig. 3B is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 27: 119, 2023; DOI: 10.3892/mmr.2023.13006].