Micronutrient Patterns and Low Intake of Vitamin A, Vitamin D, Folate, Magnesium, and Potassium Among Prediabetes and Type 2 Diabetes Patients.

Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk of diabetes-related complications. The study's objectives were to evaluate micronutrient intake in prediabetes (PD) and type 2 diabetes (T2DM) patients compared to recommended dietary intakes (RDI) and to determine the associations between the micronutrient patterns and both anthropometric measurements and biomarkers of diabetes. Methods This cross-sectional study was conducted on 349 patients with T2DM and 252 patients with PD. Micronutrient intake was evaluated using a validated food frequency questionnaire. Micronutrient patterns were extracted from factor analysis using principal component analysis with varimax rotation. Participants in the highest tertile were considered to have the highest adherence to the corresponding micronutrient pattern. Results T2DM patients had a significantly lower intake of vitamin E (9.4 ± 0.2 vs. 10.1 ± 0.3 mg; p = 0.048), vitamin D (44.3 ± 1.1 vs. 48.9 ± 1.7 IU; p = 0.020), and thiamin (1.3 ± 0.1 vs. 1.4 ± 0.1 mg; p = 0.013) compared to PD patients. All patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium and a significantly higher intake of vitamin B12 and copper compared to RDI. Three distinct micronutrient patterns were identified within each group. In the PD group, the Fe-Mn-Se pattern correlated significantly with waist circumference (WC) and fasting plasma glucose (FPG). The Vit.C-K-Folate pattern showed significant associations with body fat (BF). The Vit.B2-P-Vit.B12 pattern was significantly linked to WC, body mass index (BMI), BF, FPG, and serum insulin (SI). For the T2DM patients, the K-Folate-Mg pattern displayed an inverse and significant association with weight and WC. The Iron-Se-Vit.B3 pattern showed a significant association with low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol. The Vit.B2-P-Ca pattern was significantly associated with fasting plasma glucose (FPG). Conclusion This study demonstrated that T2DM patients had significantly lower vitamin E, vitamin D, and thiamin intake than PD patients. Both T2DM and PD patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium compared to the RDI. Among the identified micronutrient patterns, only the K-Folate-Mg pattern exhibited a significant association with reduced body weight and WC.

Influence of Bariatric Surgery on Gut Microbiota Composition and Its Implication on Brain and Peripheral Targets.

Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.

Understanding the Interplay of Dietary Intake and Eating Behavior in Type 2 Diabetes.

Diet and eating behavior both play a crucial role in the prevention and management of type 2 diabetes mellitus (T2DM). The main objective of this study was to investigate the relationship between dietary intake and eating behavior in a population of patients with T2DM. A cross-sectional study was performed using 416 patients with T2DM and their dietary intake and eating behavior were assessed with validated questionnaires. Women scored significantly higher than men for emotional and restrained eating (p < 0.001). Correlation analyses showed that emotional eaters consumed significantly more calories (r = 0.120, p = 0.014) and fat (r = 0.101, p = 0.039), as well as non-alcoholic beverages for women (r = 0.193, p = 0.003) and alcohol for men (r = 0.154, p = 0.038). Also, individuals who ate based on external cues consumed significantly more calories (r = 0.188, p < 0.001) and fat (r = 0.139, p = 0.005). These results demonstrate that eating behavior influences dietary intake. Understanding this relationship could optimize diabetes management and allow for more individualized nutritional guidance.

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID's effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.

Nutrition at the Intersection between Gut Microbiota Eubiosis and Effective Management of Type 2 Diabetes.

Nutrition is one of the most influential environmental factors in both taxonomical shifts in gut microbiota as well as in the development of type 2 diabetes mellitus (T2DM). Emerging evidence has shown that the effects of nutrition on both these parameters is not mutually exclusive and that changes in gut microbiota and related metabolites such as short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) may influence systemic inflammation and signaling pathways that contribute to pathophysiological processes associated with T2DM. With this background, our review highlights the effects of macronutrients, carbohydrates, proteins, and lipids, as well as micronutrients, vitamins, and minerals, on T2DM, specifically through their alterations in gut microbiota and the metabolites they produce. Additionally, we describe the influences of common food groups, which incorporate varying combinations of these macronutrients and micronutrients, on both microbiota and metabolic parameters in the context of diabetes mellitus. Overall, nutrition is one of the first line modifiable therapies in the management of T2DM and a better understanding of the mechanisms by which gut microbiota influence its pathophysiology provides opportunities for optimizing dietary interventions.

Risks of obesity and diabetes development in the population of the Ivano-Frankivsk region in Ukraine.

The epidemic of obesity that parallels diabetes mellitus and its complications are diseases of major concern to modern societies. Community-based screening is an effective strategy to identify people at high risk of developing overweight, obesity, prediabetes, diabetes, and related health problems. Here, we present the results of screening the population of four locations in the Ivano-Frankivsk region (Western Ukraine). The study group consisted of 400 adults and 252 children. The measured parameters were: (1) main vital signs - body temperature, resting heart rate, blood pressure; (2) anthropometric indicators - body mass and height, body mass index, waist circumference; and (3) metabolic parameters - fasting capillary blood glucose, total body fat, visceral fat, physical activity level and 10-year risk of developing type 2 diabetes. The study found that 23 % of the adults were overweight and 14.8 % obese. Among children, 9.9 % were overweight and 8.7 % obese. Adult body mass index correlated with visceral fat percentage, systolic/diastolic blood pressure and levels of fasting capillary blood glucose. Adults over 18 years of age had fasting capillary blood glucose ≥5.6 mmol/L (14.3 %), including those with undiagnosed pre-diabetes (13.3 %) and suspected diabetes mellitus (1.0 %). The percentage of visceral body fat in adults was positively associated with the 10-year risk of developing type 2 diabetes.

Dietary Fat Modulation of Gut Microbiota and Impact on Regulatory Pathways Controlling Food Intake.

Obesity is a multifactorial disease that continues to increase in prevalence worldwide. Emerging evidence has shown that the development of obesity may be influenced by taxonomic shifts in gut microbiota in response to the consumption of dietary fats. Further, these alterations in gut microbiota have been shown to promote important changes in satiation signals including gut hormones (leptin, ghrelin, GLP-1, peptide YY and CCK) and orexigenic and anorexigenic neuropeptides (AgRP, NPY, POMC, CART) that influence hyperphagia and therefore obesity. In this review, we highlight mechanisms by which gut microbiota can influence these satiation signals both locally in the gastrointestinal tract and via microbiota-gut-brain communication. Then, we describe the effects of dietary interventions and associated changes in gut microbiota on satiety signals through microbiota-dependent mechanisms. Lastly, we present microbiota optimizing therapies including prebiotics, probiotics, synbiotics and weight loss surgery that can help restore beneficial gut microbiota by enhancing satiety signals to reduce hyperphagia and subsequent obesity. Overall, a better understanding of the mechanisms by which dietary fats induce taxonomical shifts in gut microbiota and their impact on satiation signaling pathways will help develop more targeted therapeutic interventions in delaying the onset of obesity and in furthering its treatment.

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats.

Alterations in dopamine neurotransmission are associated with obesity and food preferences. Otsuka Long-Evans Tokushima Fatty (OLETF) rats that lack functional cholecystokinin receptor type-1 (CCK-1R), due to a natural mutation, exhibit impaired satiation, are hyperphagic, and become obese. In addition, compared to lean control Long-Evans Tokushima (LETO) rats, OLETF rats have pronounced avidity for over-consuming palatable sweet solutions, have greater dopamine release to psychostimulants, reduced dopamine 2 receptor (D2R) binding, and exhibit increased sensitivity to sucrose reward. This supports altered dopamine function in this strain and its general preference for palatable solutions such as sucrose. In this study, we examined the relationship between OLETF's hyperphagic behavior and striatal dopamine signaling by investigating basal and amphetamine stimulated motor activity in prediabetic OLETF rats before and after access to sucrose solution (0.3 M) compared to non-mutant control LETO rats, as well as availability of dopamine transporter (DAT) using autoradiography. In the sucrose tests, one group of OLETF rats received ad libitum access to sucrose while the other group received an amount of sucrose equal to that consumed by the LETO. OLETFs with ad libitum access consumed significantly more sucrose than LETOs. Sucrose exerted a biphasic effect on basal activity in both strains, i.e., reduced activity for 1 week followed by increased activity in weeks 2 and 3. Basal locomotor activity was reduced (-17%) in OLETFs prior to sucrose, compared to LETOs. Withdrawal of sucrose resulted in increased locomotor activity in both strains. The magnitude of this effect was greater in OLETFs and the activity was increased in restricted compared to ad-libitum-access OLETFs. Sucrose access augmented AMPH-responses in both strains with a greater sensitization to AMPH during week 1, an effect that was a function of the amount of sucrose consumed. One week of sucrose withdrawal sensitized AMPH-induced ambulatory activity in both strains. In OLETF with restricted access to sucrose, withdrawal resulted in no further sensitization to AMPH. DAT availability in the nucleus accumbens shell was significantly reduced in OLETF compared with aged-matched LETO. Together, these findings show that OLETF rats have reduced basal DA transmission and a heightened response to natural and pharmacological stimulation.

Dietary Patterns of Patients with Prediabetes and Type 2 Diabetes.

Given the worldwide high prevalence of type 2 diabetes, the prevention and control of this disease has become an urgent priority. In this research, we report the results from a cross-sectional study conducted in the counties of Suceava and Iasi, northeast of Romania, on 587 patients with type 2 diabetes and 264 patients with prediabetes. By employing a factor analysis (principal component) on 14 food groups followed by varimax orthogonal rotation, three dietary patterns were identified for each group. In prediabetes, a low adherence to a specific dietary pattern (1 and 2) was associated with lower fasting plasma glucose, blood pressure and serum insulin, compared to increased adherence. In patients with diabetes, a low adherence to Pattern 1 was associated with lower systolic blood pressures, while a low adherence to Pattern 3 was associated with a lower HbA1c, compared to high adherence. Statistically significant differences between the groups were observed for fats and oils, fish and fish products, fruit, potatoes, sugars, preserves and snacks intake. The study demonstrated that certain food patterns are associated with increased blood pressure, fasting blood glucose and serum insulin.

Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.

Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as therapeutic modalities in prevention of cardiovascular disease. Overall, understanding the mechanisms by which gut microbiota and their metabolites affect dyslipidemia progression will help develop more precise therapeutic targets to optimize lipid metabolism.

Long COVID: Molecular Mechanisms and Detection Techniques.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols.

Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.

The Use of Biopolymers as a Natural Matrix for Incorporation of Essential Oils of Medicinal Plants.

The benefits of using biopolymers for the development of films and coatings are well known. The enrichment of these material properties through various natural additions has led to their applicability in various fields. Essential oils, which are well-known for their beneficial properties, are widely used as encapsulating agents in films based on biopolymers. In this study, we developed biopolymer-based films and tested their properties following the addition of 7.5% and 15% (w/v) essential oils of lemon, orange, grapefruit, cinnamon, clove, chamomile, ginger, eucalyptus or mint. The samples were tested immediately after development and after one year of storage in order to examine possible long-term property changes. All films showed reductions in mass, thickness and microstructure, as well as mechanical properties. The most considerable variations in physical properties were observed in the 7.5% lemon oil sample and the 15% grapefruit oil sample, with the largest reductions in mass (23.13%), thickness (from 109.67 µm to 81.67 µm) and density (from 0.75 g/cm3 to 0.43 g/cm3). However, the microstructure of the sample was considerably improved. Although the addition of lemon essential oil prevented the reduction in mass during the storage period, it favored the degradation of the microstructure and the loss of elasticity (from 16.7% to 1.51% for the sample with 7.5% lemon EO and from 18.28% to 1.91% for the sample with 15% lemon EO). Although the addition of essential oils of mint and ginger resulted in films with a more homogeneous microstructure, the increase in concentration favored the appearance of pores and modifications of color parameters. With the exception of films with added orange, cinnamon and clove EOs, the antioxidant capacity of the films decreased during storage. The most obvious variations were identified in the samples with lemon, mint and clove EOs. The most unstable samples were those with added ginger (95.01%), lemon (92%) and mint (90.22%).

Gut Microbiota Restores Central Neuropeptide Deficits in Germ-Free Mice.

Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in germ-free (GF) animals, especially leptin, which is strikingly low in these animals. Therefore, we aimed to determine the response to exogenous leptin in GF mice as compared to conventionally raised (CONV-R) mice. Specifically, we injected and measured serum leptin in both GF and CONV-R mice and measured expression of orexigenic and anorexigenic peptides NPY, AgRP, POMC, and CART in the hypothalamus and hindbrain to examine whether the GM has an impact on central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA, while mRNA expression of POMC and CART remained unchanged. Administration of leptin normalized circulating levels of leptin, GLP-1, PYY, and ghrelin, all of which were significantly decreased in GF mice. Finally, brief conventionalization of GF mice for 10 days restored the deficits in hypothalamic and hindbrain neuropeptides present in GF animals. Taken together, these results show that the GM regulates hypothalamic and hindbrain orexigenic/anorexigenic neuropeptide expression. This is in line with the role of gut microbiota in lipid metabolism and fat deposition that may contribute to excess fat in conventionalized animals under high feeding condition.

Impact of Nutrition, Microbiota Transplant and Weight Loss Surgery on Dopaminergic Alterations in Parkinson's Disease and Obesity.

Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra pars compacta of the midbrain. Emerging evidence has shown that dietary intake affects the microbial composition in the gut, which in turn contributes to, or protects against, the degeneration of dopaminergic neurons in affected regions of the brain. More specifically, the Mediterranean diet and Western diet, composed of varying amounts of proteins, carbohydrates, and fats, exert contrasting effects on PD pathophysiology via alterations in the gut microbiota and dopamine levels. Interestingly, the negative changes in the gut microbiota of patients with PD parallel changes that are seen in individuals that consume a Western diet, and are opposite to those that adhere to a Mediterranean diet. In this review, we first examine the role of prominent food groups on dopamine bioavailability, how they modulate the composition and function of the gut microbiota and the subsequent effects on PD and obesity pathophysiology. We then highlight evidence on how microbiota transplant and weight loss surgery can be used as therapeutic tools to restore dopaminergic deficits through optimizing gut microbial composition. In the process, we revisit dietary metabolites and their role in therapeutic approaches involving dopaminergic pathways. Overall, understanding the role of nutrition on dopamine bioavailability and gut microbiota in dopamine-related pathologies such as PD will help develop more precise therapeutic targets to rescue dopaminergic deficits in neurologic and metabolic disorders.

Do Diet and Dietary Supplements Mitigate Clinical Outcomes in COVID-19?

The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authorities and citizens around the globe are still grappling with to this day. While public health measures, vaccine development, and new therapeutics have made great strides in understanding and managing the pandemic, there has been an increasing focus on the potential roles of diet and supplementation in disease prevention and adjuvant treatment. In the literature, the impact of nutrition on other respiratory illnesses, including the common cold, pneumonia, and influenza, has been widely demonstrated in both animal and human models. However, there is much less research on the impact related to COVID-19. The present study discusses the potential uses of diets, vitamins, and supplements, including the Mediterranean diet, glutathione, zinc, and traditional Chinese medicine, in the prevention of infection and severe illness. The evidence demonstrating the efficacy of diet supplementation on infection risk, disease duration, severity, and recovery is mixed and inconsistent. More clinical trials are necessary in order to clearly demonstrate the contribution of nutrition and to guide potential therapeutic protocols.

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer's Disease.

It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer's disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal ß-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of ß-amyloid peptide to form ß-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of ß-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in ameliorating type 2 diabetes mellitus symptoms. Furthermore, both diabetes and neurodegenerative conditions, such as AD, are characterized by chronic inflammatory responses accompanied by the presence of dysregulated inflammatory biomarkers. This review presents current evidence describing the role of various small bioactive molecules known to ameliorate amyloidosis and subsequent effects in prevention and development of diabetes and AD. It also highlights the potential efficacy of peptide-drug conjugates capable of targeting intracellular targets.

Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling.

Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus-pituitary-adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium,Enterococcus, and Ruminococcus and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson's disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders.

The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes.

Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 has been shown to be a more sensitive marker for periodontal inflammation during orthodontic treatment, which opens new perspectives in reducing periodontal hazards during such treatments. Both MMP-8 and MMP-9 are extremely valuable diagnostic tools in treating periodontitis, and future studies and healthcare policies should focus on implementing more accessible methods of chairside testing in order to reduce the prevalence of this disease.

A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19.

The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69-70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.