The gut microbiota coevolves with its host, and numerous factors like diet, lifestyle, drug intake and geographical location continuously modify its composition, deeply influencing host health. ...Recent studies demonstrated that gut dysbiosis can alter normal brain function through the so‐called gut–brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, thus playing a key role in the pathogenesis of neurodegenerative disorders, such as Alzheimer’s disease (AD). In this perspective, in the constant search for novel treatments in AD, the rational modulation of gut microbiota composition could represent a promising approach to prevent or delay AD onset or to counteract its progression. Preclinical and human studies on microbiota modulation through oral bacteriotherapy and faecal transplantation showed anti‐inflammatory and antioxidant effects, upregulation of plasma concentration of neuroprotective hormones, restoration of impaired proteolytic pathways, amelioration of energy homeostasis with consequent decrease of AD molecular hallmarks and improvement of behavioural and cognitive performances. In this review, we dissect the role of gut microbiota in AD and highlight recent advances in the development of new multitarget strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD.
This review deals with recent advances in the development of new multitarget strategies for gut microbiota modulation as preventative and therapeutic approaches in Alzheimer’s disease (AD) focusing on the molecular mechanisms involved. Preclinical and human studies on microbiota manipulation through oral bacteriotherapy and faecal transplantation showed anti‐inflammatory and antioxidant effects, upregulation of neuroprotective hormones, restoration of impaired proteolysis, amelioration of energy homeostasis with consequent reduction of AD hallmarks and dementia.
Peroxiredoxins (PRDXs) are antioxidant enzymes, known to catalyze peroxide reduction to balance cellular hydrogen peroxide (H2O2) levels, which are essential for cell signaling and metabolism and act ...as a regulator of redox signaling. Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Early studies demonstrated that PRDXs regulates cell growth, metabolism and immune regulation and therefore involved in the pathologic regulator or protectant of several cancers, neurodegenerative diseases and inflammatory diseases. Oxidative stress and antioxidant systems are important regulators of redox signaling regulated diseases. In addition, thiol-based redox systems through peroxiredoxins have been demonstrated to regulate several redox-dependent process related diseases. In this review article, we will discuss recent findings regarding PRDXs in the development of diseases and further discuss therapeutic approaches targeting PRDXs. Moreover, we will suggest that PRDXs could be targets of several diseases and the therapeutic agents for targeting PRDXs may have potential beneficial effects for the treatment of cancers, neurodegenerative diseases and inflammatory diseases. Future research should open new avenues for the design of novel therapeutic approaches targeting PRDXs.
Tuberculosis is an intracellular infectious disease caused by Mycobacterium tuberculosis, which mainly affects the lungs. Especially in patients infected by the Human Immunodeficiency Virus (HIV) or ...other immunosuppressed patients, tuberculosis is considered one of the infectious diseases with higher morbidity and mortality rates. Despite considerable improvements in diagnosis and treatment during the last decades, the drugs currently used in tuberculosis treatment still have limitations, such as low plasma levels after oral administration, low solubility in water, fast metabolization by the liver with a short 1/2 life and low patient adherence to treatment. Another limiting point is drug-resistant strains. Thus, to overcome such limitations, nanotechnology emerges as a promising alternative due to the drug release systems and its recent advances that show potential improvements, such as improved bioavailability and reduction of the therapeutic dose. In this context, this manuscript aimed to highlight the nanotechnology-based drug delivery systems studies pointing to those most effective for tuberculosis treatment. Studies based on polymeric nanoparticles are promising in diagnosing, treating, and even preventing tuberculosis because they have the high stability and transport capacity of these drugs. Solid lipid nanoparticles are another type of promising nanocarriers for treating tuberculosis, mainly for delivering drugs to the remote lymphatic system. Other promising nanosystems are the liposomes, since they have also shown efficacy in significantly reducing bacterial load compared to conventional drug administration. Given the results presented, the administration of drugs through nanotechnology-based drug delivery systems has benefits in treating tuberculosis since in vitro and in vivo studies have revealed that nanotechnology through nano- and micro-scale systems is an effective and promising approach for the treatment of tuberculosis. Furthermore, the increase in the number of patents for nanosystems aimed at treating TB has demonstrated researchers' commitment in the quest to improve the therapeutic arsenal against tuberculosis.
Display omitted
Mutations in Munc18‐1/STXBP1 (syntaxin‐binding protein 1) are linked to various severe early epileptic encephalopathies and neurodevelopmental disorders. Heterozygous mutations in the STXBP1 gene ...include missense, nonsense, frameshift, and splice site mutations, as well as intragenic deletions and duplications and whole‐gene deletions. No genotype–phenotype correlation has been identified so far, and patients are treated by anti‐epileptic drugs because of the lack of a specific disease‐modifying therapy. The molecular disease mechanisms underlying STXBP1‐linked disorders are yet to be fully understood, but both haploinsufficiency and dominant‐negative mechanisms have been proposed. This review focuses on the current understanding of the phenotypic spectrum of STXBP1‐linked disorders, as well as discusses disease mechanisms in the context of the numerous pathways in which STXBP1 functions in the brain. We additionally evaluate the available animal models to study these disorders and highlight potential therapeutic approaches for treating these devastating diseases.
STXBP1 is essential for neuronal communication. Mutations in STXBP1 cause neuronal dysfunction, leading to epilepsy, intellectual disability, developmental delay, autism spectrum disorders, and motor disturbances. Both haploinsufficiency and a dominant‐negative activity have been proposed as underlying disease mechanism. Therapeutic strategies aim at suppressing the epileptic activity, modulating STXBP1 expression on an mRNA level, preventing formation of non‐productive SNARE‐complexes, and boosting STXBP1 folding and thereby functional STXBP1 levels via chemical and pharmacological chaperones.
Noncoding RNAs (ncRNAs) represent a large segment of the human transcriptome and have been shown to play important roles in cellular physiology and disease pathogenesis. Increasing evidence on the ...functional roles of ncRNAs in cancer progression emphasizes the potential of ncRNAs for cancer treatment. Here, we summarize the roles of ncRNAs in disease relapse and resistance to current standard chemotherapy and radiotherapy; the current research progress on ncRNAs for clinical and/or potential translational applications, including the identification of ncRNAs as therapeutic targets; therapeutic approaches for ncRNA targeting; and ncRNA delivery strategies in potential clinical translation. Several ongoing clinical trials of novel RNA-based therapeutics were also emphasized. Finally, we discussed the perspectives and obstacles to different target combinations, delivery strategies, and system designs for ncRNA application. The next approved nucleic acid drug to treat cancer patients may realistically be on the horizon.
Colorectal cancer (CRC) is one of the most lethal human malignancies, and with the growth of societies and lifestyle changes, the rate of people suffering from it increases yearly. Important factors ...such as genetics, family history, nutrition, lifestyle, smoking, and alcohol can play a significant role in increasing susceptibility to this cancer. On the other hand, the metabolism of several macromolecules is also involved in the fate of tumors and immune cells. The evidence discloses that cholesterol and its metabolism can play a role in the pathogenesis of several cancers because there appears to be an association between cholesterol levels and CRC, and cholesterol-lowering drugs may reduce the risk. Furthermore, changes or mutations of some involved genes in cholesterol metabolism, such as CYP7A1 as well as signaling pathways, such as mitogen-activated protein kinase (MAPK), can play a role in CRC pathogenesis. This review summarized and discussed the role of cholesterol in the pathogenesis of CRC as well as available cholesterol-related therapeutic approaches in CRC.
The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is ...characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines-blocking transmission and antiviral therapy-inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother-to-child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.
Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with ...antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.
As climate change worsens and public awareness of its grave impact increases, individuals are increasingly experiencing distressing mental health symptoms which are often grouped under the umbrella ...term of eco-anxiety. Clear guidance is needed to enable mental health professionals to make informed choices of appropriate interventions and approaches in their eco-anxiety treatment plans. A scoping review was conducted to examine the current understanding of eco-anxiety and related intervention options and recommendations. The review included 34 records, 13 of which reflected specific psychological approaches. A thematic analysis of the content of the selected records yielded five major themes across interventions for individual and group treatment of eco-anxiety: practitioners’ inner work and education, fostering clients’ inner resilience, encouraging clients to take action, helping clients find social connection and emotional support by joining groups, and connecting clients with nature. Recommendations for treatment plans are to focus on holistic, multi-pronged, and grief-informed approaches that include eco-anxiety focused group work.
PDF
