BACKGROUND: This review summarizes recent findings in molecular biology and neuroimaging and their applicability to the classification and identification of depression. We discuss whether there is reliable evidence that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as well as the selection of treatments. OBJECTIVE: The purpose of this investigation is to present molecular mechanisms that contribute to different origins of depressions that could prove useful in the daily psychiatric clinic-based practices. METHODS: The authors have analyzed and summarized electronic publications available in PubMed, Science Direct, Google Scholar, and Scopus. RESULTS: The introduction of molecular diagnostic methods into medical practice is a promising method to improve the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes of depression. CONCLUSION: Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity, subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression. Additional focused research should be continued with respect to the molecular and genetic biology of different types of depression. There already are promising findings, but additional research to define biologically based depressive subtypes is needed and worthwhile.

BACKGROUND: Suicide is a major public health problem on a global scale, with about 800.000 deaths every year. In particular, it represents one of the main causes of death among adolescents and young adults aged between 15 and 29 years. The World Health Organization (WHO) describes suicide as "an act of deliberate killing" and that is placed at the extreme end of the continuous spectrum of suicidal behaviors (SBs). These include suicidal ideation, attempted suicide and suicide itself. OBJECTIVE: The aim of the present review was to better clarify the suicide vulnerability genetic biomarkers and genetic variants correlated with the response to lithium and clozapine and to evaluate some correspondences. METHODS: We reviewed the current literature, focusing our attention on genetic molecular studies about neurobiological systems involved in SBs and pharmacogenetic studies about antisuicidal drugs (lithium and clozapine). RESULTS: The studies that we have reviewed have shown mixed results. Interestingly, rs1800532 polymorphism of the SLC6A4 gene, encoding for the serotonin transporter, is potentially correlated with both suicide vulnerability and a poor response to lithium and clozapine. CONCLUSION: Due to the impact of suicide on public health, more studies are needed to open a promising route to prevent suicide in personalized and precise psychiatry.

The rapid pattern of population ageing in recent years increases the risk of appearance of associated neurodegenerative diseases. Dementias are one of the most feared disorders, and although not necessarily all elderly people have dementia, the number of people with this disease is increasing rapidly. The causes of dementia are multiple, and the diagnosis of the different types of dementia is complicated since most patients display mixed dementias and symptoms overlapping. Personalized diagnosis and treatments would be desirable, but this requires a deep knowledge of each type of dementia where a multidisciplinary approach would be ideal. Thus, the aim of this review is to summarize the features of the main types of dementia as well as to compilate the more recent findings on this subject, ranging from genetic and molecular studies to animal models, including the use of omics platforms based on powerful hybrid instrumental techniques, and neuroimage techniques. On the other hand, we consider the aspects that can prevent these disorders and depend on modifiable factors, such as diet, among others. Finally, new technologies, such as nanotechnology can provide novel strategies for the administration of effective treatments. In this regard, our purpose is to provide the most updated and complete overview of state of the art about characteristics of these disorders.

BACKGROUND: The rapid eruption of Coronavirus at the end of 2019 has caused global health crisis and significant loss to the economy and social well-being. This created a massive shortage of advanced health facilities with inadequate medicinal supply, further deteriorating human health conditions. On the basis of adverse effects of the ongoing pandemic, this review has been proposed to evaluate the antiviral efficacy of plant- based therapeutics, against SARS-CoV-2 (commonly called COVID-19) infection. It highlights the possible action of the mechanism of phytotherapeutic drugs against coronavirus inhibition, further validated by clinical trials on herbal formulas is reviewed. Though the experimental studies on COVID-19 treatment are limited, the undesirable side effects of herbal drugs and unidentified compounds cannot be ignored. OBJECTIVE: We have made an effort to study the prospective plant-derived bioactive entities and their effectiveness in the treatment of COVID-19 and also emphasize on safety and regulatory concerns of phytomedicines. METHODS: The methodology involves relevant studies on COVID-19 treatment based on herbal extracts and the purified bioactive metabolites. The e-literature survey has been done by downloading research articles available on PubMed (National Library of medicine), Elsevier, and Google scholar search engines. The keywords used are plant metabolites, natural bioactive, phytotherapeutic drugs, clinical trials, SARS-CoV-2, Coronavirus inhibitors and herbal extracts. RESULTS: The review pays particular attention to the etiological study of the COVID-19 virus and its inhibition using medicinal plant metabolites as immunomodulatory agents. The application of valuable bioactives like phenolic compounds, saponins, alkaloids, tannins, flavonoids and terpenoids in preparing herbal formula/drug has been focused on. The drug resistance of bioactive compounds and their side effects on human health were discussed for effective phytomedicine, thus, emphasizing the perspectives of phytotherapeutic drugs as a safe remedy to boost immunomodulatory functions and antiviral activity against COVID-19. CONCLUSION: Altogether, the review presents the action mechanism of plant extracts rich in bioactive compounds and depicted potential antiviral activity against SARS-CoV-2. These plant bioactive compounds can serve as lead molecules to develop phytomedicine, ensuring all safety regulations in the clinical trials to treat or prevent COVID-19 viral infections.

BACKGROUND: A patient was evaluated with respect to the effects and results of a complex treatment plan for complete dental rehabilitation. Several steps were required. Each step included immunological tests of salivary biomarkers. Clinical and immunological assessments were evaluated on Day 3, Week 2, Month 3, and Month 6 post-surgery. These evaluations guided the decision-making process with regard to preparation of a permanent prosthesis. OBJECTIVE: The aim of the study is to evaluate the response of tissues and organs of the maxillofacial region in patients during dental rehabilitation after maxillofacial surgery. METHODS: Complex treatment and rehabilitation involving cooperation between the specialists in maxillofacial surgery, prosthetic dentistry, and cancer immunology. RESULTS: Long-term monitoring and clinical examination showed a direct relationship between the patient's clinical and dental status and the changes in oral fluid biomarkers. CONCLUSION: The data revealed that the oral fluid biomarkers reflected the patient's adaptation to prosthodontic rehabilitation. Treatment and monitoring of a maxillofacial tumor patient could use biomarkers as a non-invasive indicator.

Leukotrienes are one of the major eicosanoid lipid mediators produced due to an oxidative transformation of arachidonic acid. Subsequently, they get converted into various cellular signaling hormones by a series of enzymes of myeloid origin to mediate or debilitate inflammation. Interestingly, the available literature demonstrates the pivotal role of eicosanoids in neurodegenerative, obesity, diabetes, cardiovascular diseases, and cancers as well. The aberrant metabolism of arachidonic acid by the LOX pathway is a common feature of epithelial-derived malignancies and suggests the contributory role of dietary fats in carcinogenesis. The enzymes and receptors of the LOX pathway play a significant role in cell proliferation, differentiation and regulation of apoptosis through multiple signaling pathways and have been reported to be involved in various cancers, including prostate, colon, lung and pancreatic cancers. So far, leukotriene receptor antagonists and 5-LOX inhibitors have reached up to the clinical trials for treating various diseases. Keeping its various roles in cancer, the review highlights the components of the leukotriene synthesizing machinery, emerging opportunities for pharmacological intervention, and the probability of considering lipoxygenases and leukotriene receptors as good candidates for clinical chemoprevention studies.

Legumain (LGMN; EC: 3.4.22.34), an asparaginyl endopeptidase (AEP) or asparaginyl carboxypeptidase (ACP), is a member of the C13 family of cysteine proteases. Elevated expression of LGMN is reported not only in the tumor cells of breast, prostate, and liver but also in the macrophages of the tumor microenvironment. Hence, LGMN is considered as a key protein involved in the regulation of tumor angiogenesis, invasion, and metastasis. Targeting LGMN using siRNA or pharmacological agents and peptides was reported to reduce cancer cell proliferation in vitro and shrink tumor size in vivo. Moreover, expression of LGMN is significantly low in normal cells compared to tumor cells or tumor-associated macrophages (TAMs); hence, legumain can be used as a marker for tumor recognition and targeting. Therefore, approaches inhibiting LGMN expression or activity are more viable, less toxic, and help in developing the targeted therapeutics. However, to date, LGMN targeting strategies have not been well reported. In this review, an attempt was made to summarize articles pertaining to LGMN (a) structure and activity; (b) oncogenic nature; (c) pharmacological inhibitors; and (d) targeting approaches that inhibit tumor growth. Furthermore, a list of existing gaps in LGMN research is highlighted, which needs additional studies.

BACKGROUND: The impact of abusive alcohol consumption on human health is remarkable. According to the World Health Organization (WHO), approximately 3.3 million people die annually because of harmful alcohol consumption (the figure represents around 5.9% of global deaths). Alcohol Use Disorder (AUD) is a chronic disease where individuals exhibit compulsive alcohol drinking and present negative emotional states when they do not drink. In the most severe manifestations of AUD, the individuals lose control over intake despite a decided will to stop drinking. Given the multiple faces and the specific forms of this disease, the term AUD often appears in the plural (AUDs). Since only a few approved pharmacological treatments are available to treat AUD and they do not apply to all individuals or AUD forms, the search for compounds that may help to eliminate the burden of the disease and complement other therapeutical approaches is necessary. METHODS: This work reviews recent research focused on the involvement of epigenetic mechanisms in the pathophysiology of AUD. Excessive drinking leads to chronic and compulsive consumption that eventually damages the organism. The central nervous system is a key target and is the focus of this study. The search for the genetic and epigenetic mechanisms behind the intricated dysregulation induced by ethanol will aid researchers in establishing new therapy approaches. CONCLUSION: Recent findings in the field of epigenetics are essential and offer new windows for observation and research. The study of small molecules that inhibit key epienzymes involved in nucleosome architecture dynamics is necessary in order to prove their action and specificity in the laboratory and to test their effectivity and safety in clinical trials with selected patients bearing defined alterations caused by ethanol.

BACKGROUND: Schizophrenia is a chronic mental illness that in 80% of cases has a genetic etiology. In the last years, 260 risk genes with a predisposition to schizophrenia have been discovered and correlations between risk genes and the therapeutic efficacy of an antipsychotic treatment/pharmacotherapy resistance have been reported. OBJECTIVE: The objective of this review is to update the main risk genes involved in schizophrenia and to establish an association between the single nucleotide polymorphisms (SNPs) of these genes and pharmacotherapy resistance/efficacy of a determined antipsychotic treatment. Besides, neural networks in the brain centers involved in schizophrenia will be updated to point out the altered functions of classical neurotransmitters and neuropeptides due to risk genes. METHODS: In schizophrenia, important risk genes, such as catechol-O-methyl transferase (COMT), monoamine oxidase (MAO A/B), glutamic acid decarboxylase 67 (GAD 67), dysbindin-1 and neuregulin-1 will be mentioned. To describe the function of these risk genes, neural networks in the ventral tegmental area, hippocampus and prefrontal cortex will also be developed. RESULTS: An association between the SNPs of some risk genes and the efficacy of an antipsychotic treatment is reported: SNPs such as rs165599 (COMT gene), rs1801028 (D2 receptor gene) and rsSer9Gly (D3 receptor gene) are associated with a better antipsychotic treatment efficacy (e.g., treatment of negative schizophrenic symptoms with risperidone). The rs4680 SNP (COMT and D2 receptor genes) is associated with antipsychoticinduced dopamine hypersensitivity and pharmacotherapy resistance. The function of risk genes is described: COMT and MAO A/B genes, with reduced activity in the corresponding enzymes, are associated with a decrease in dopamine degradation and hence dopamine hyperactivity occurred via D2 receptors. The GAD 67 risk gene is linked with GABAergic dysfunction and consequently GABAergic neurons weakly presynaptically inhibit D2 dopaminergic neurons. The D-amino acid oxidase activator (DAOA) risk gene is connected with glutamatergic dysfunction via NMDA receptors. Glutamatergic neurons might exert a weak presynaptic inhibition upon 5- HT2A serotonergic neurons located in the ventral tegmental area and hippocampus. Neural networks in the latter two regions and in the prefrontal cortex are updated. CONCLUSION: It is important to examine the SNPs of the risk genes involved in schizophrenia to establish a correlation between these SNPs and the efficacy of a determined antipsychotic drug. In the future, after examining these SNPs, it might be possible to choose the most appropriate antipsychotic drug. Thus, schizophrenic patients with a good response to a determined antipsychotic treatment and patients with resistance to this treatment could be well differentiated.

Coronavirus disease (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is a positive single-stranded RNA virus having a large genome ~30 kb. SARSCoV- 2 is zoonotic and highly contagious, causing severe pneumonia-like symptoms. The efficacy of the different potential drug and drug candidates against COVID-19 has been investigated, which are under various stages of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated in the prevention and therapy of COVID-19. The plant produces secondary metabolites in response to viral infection. Different classes of secondary metabolites have different mechanisms to counter virus attacks. Many nanomaterials produced by carbohydrates and lipids have been exploited for their in-vitro and in-vivo delivery of antiviral therapeutics. The vaccine has shown impressive results in producing antibodies against SARS-CoV2 and has been evaluated for safety, tolerance, and preliminary immunogenicity. Similarly, DNA/RNA-based therapy has shown high clinical significance. Various forms of vitamins, minerals, herbs, and phytonutrients help to enhance immunity and be implicated in the control of COVID-19. However, such measures should not replace social distancing, quarantine and special care.

Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures that are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in MS research is to find treatments which allow the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and their use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies that have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as "myelin sheath", "remyelination", "demyelination", "oligodendrocyte" and "lipid synthesis" were used to focus the search. We preferred papers published after January 2015, but did not exclude earlier seminal papers.