Novel therapeutical approaches based on neurobiological and genetic strategies for diabetic polyneuropathy - A review.

BACKGROUND: Neuropathy is among the most often reported consequences of diabetes and the biggest cause of morbidity and mortality in people suffering from this life-long disease. Although different therapeutic methods are available for diabetic neuropathy, it is still the leading cause of limb amputations, and it significantly decreases patients' quality of life. AIM: This study investigates potential novel therapeutic options that could ameliorate symptoms of DN. METHODOLOGY: Research and review papers from the last 10 years were taken into consideration. RESULTS: There are various traditional drugs and non-pharmacological methods used to treat this health condition. However, the research in the area of pathogenic-oriented drugs in the treatment of DN showed no recent breakthroughs, mostly due to the limited evidence about their effectiveness and safety obtained through clinical trials. Consequently, there is an urgent demand for the development of novel therapeutic options for diabetic neuropathy. CONCLUSION: Some of the latest novel diagnostic methods for diagnosing diabetic neuropathy are discussed as well as the new therapeutic approaches, such as the fusion of neuronal cells with stem cells, targeting gene delivery and novel drugs.

Effects of Zofenopril on Arterial Stiffness in Hypertension Patients.

Angiotensin-converting enzyme inhibitors (ACEIs) reduce arterial stiffness beyond their antihypertensive effect. Studies showed that sulfhydryl ACEIs have the antioxidative potential to improve endothelial function, which might have a clinical effect on arterial distensibility. However, there are no studies that directly compare the effects of sulfhydryl (zofenopril) and non-sulfhydryl ACEIs (enalapril) on arterial stiffness. Therefore, this prospective study aims to compare the effects of enalapril and zofenopril on arterial stiffness and oxidative stress in both short- and long-term treatment of arterial hypertension (AH). Baseline and post-treatment peripheral and central arterial pressure indices, augmentation index (Aix), aortic pulse wave velocity (ao-PWV), serum levels of oxidized low-density cholesterol lipoprotein, LDL and uric acid (UA) were measured. The results showed that acute treatment with zofenopril, in contrast to enalapril, significantly decreased peripheral and central Aix (p < 0.001). Chronic treatment with zofenopril showed a superior effect over enalapril on the reduction of the peripheral systolic arterial pressure with reduction of ao-PWV (p = 0.004), as well as a reduction in peripheral Aix (p = 0.021) and central Aix (p = 0.021). Therefore, this study indicates that zofenopril has beneficial effects on the reduction of arterial stiffness compared to enalapril. It has potent clinical efficacy in AH treatment and further studies should compare its safety and long-term efficacy to other AH drugs that would aid clinicians in treating AH and other various cardiovascular diseases that have arterial stiffness as a common denominator.

Effect of Diabetic Neuropathy on Reparative Ability and Immune Response System.

The effects of diabetes can be divided into short, medium and long term and various human organ systems can be effected. The present study aimed to determine how much the duration of diabetes mellitus (DM) affect the reparative ability of the body, immune response and the development of DM complications. Interleukin 1-ß (IL-1ß) and Interleukin 6 (IL-6) were monitored as specific indicators of inflammatory reaction and C-reactive protein (CRP), leukocyte count (WBC) and sedimentation rate (ESR) as general markers of inflammatory reaction. Tumour necrosis factor α (TNF-α) and transforming growth factor ß1 (TGF-ß1) were observed as indicators of reparative ability and polyneuropathy. All interleukins were determined by ELISA and evaluated spectrophotometrically. Michigan Neuropathy Screening Instrument (MNSI) is performed for neuropathy examination. Patients with diabetes mellitus were divided into 3 groups, according to duration of diabetes mellitus. IL-6 levels correlated with clinical stage of diabetic polyneuropathy at p = 0.025 R = 0.402; with CRP at p = 0.0001, R = 0.784 as well as correlation of CRP and MNSI score (R = 0.500, p = 0.034) in a group of patients with DM lasting up to 10 years. The reparative ability of the body is reduced by physiological age and ages of DM duration. The immune response is weakened in DM additionally. The dual activity of cytokines IL-6 and TGF-ß1 is present in long-duration Diabetes Mellitus.

Nanostructured Materials for Drug Delivery and Tissue Engineering Applications.

Nanotechnology and nanostructured materials for drug delivery and tissue engineering applications are relatively new field that is constantly advancing and expanding. The materials used are at the nanoscale level. Recently, great discoveries and applications have been made (Agents for use in chemotherapy, biological agents and immunotherapy agents) in the treatment of diseases in various areas. Tissue engineering is based on the regeneration and repair of damaged organs and tissues by developing biological substitutes that restore, maintain or improve the function of tissues and organs. Cells isolated from patients are used to seed 3D nanoparticles that can be synthetic or natural biomaterials. For the development of new tissue in tissue engineering, it is necessary to meet the conditions for connecting cells. This paper will present the ways of connecting cells and creating new tissues. Some recent discoveries and advances in the field of nanomedicine and the application of nanotechnology in drug delivery will be presented. Furthermore, the improvement of the effectiveness of new and old drugs based on the application of nanotechnology will be shown.

Cellular therapeutic potential of genetically engineered stem cells in cancer treatment.

Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

Functional biotransformation of phytoestrogens by gut microbiota with impact on cancer treatment.

The human gut is a host for trillions of microorganisms, divided into more than 3,000 heterogeneous species that is called the gut microbiota. The gut microbiota composition can be altered by many different endogenous and exogenous factors, especially diet and nutrition. A diet rich in phytoestrogens, a variable group of chemical compounds similar to 17-ß-estradiol (E2), the essential female steroid sex hormone is potent to change the composition of gut microbiota. However, the metabolism of phytoestrogens also highly depends on the action of enzymes produced by gut microbiota. Novel studies have shown that phytoestrogens could play an important role in the treatment of different types of cancers, such as breast cancer in women, due to their potential to decrease estrogen levels. This review aims to summarize recent findings about the lively dialogue between phytoestrogens and gut microbiota and to address their possible future application, especially in treating patients with diagnosed breast cancer. A potential therapeutic approach for the prevention and improving outcomes in breast cancer patients could be based on targeted probiotic supplementation with the use of soy phytoestrogens. A positive effect of probiotics on the outcome and survival of patients with breast cancer has been established. However, more in vivo scientific studies are needed to pave the way for the use of probiotics and phytoestrogens in the clinical practice of breast cancer treatment.

Covid-19 a triggering factor of autoimmune and multi-inflammatory diseases.

SARS-CoV-2 virus has attracted a lot of attention globally due to the autoimmune and inflammatory processes that were observed during the development of Covid-19 disease. Excessive activation of immune response and triggering of autoantibodies synthesis as well as an excessive synthesis of inflammatory cytokines and the onset of cytokine storm has a vital role in the disease outcome and the occurring autoimmune complications. This scenario is reminiscent of infiltration of lymphocytes and monocytes in specific organs and the increased production of autoantibodies and chemoattractants noted in other inflammatory and autoimmune diseases. The main goal of this study is to investigate the complex inflammatory processes that occur in Covid-19 disease and to find similarities with other inflammatory diseases such as multiple sclerosis (MS), acute respiratory distress syndrome (ARDS), rheumatoid arthritis (RA) and Kawasaki syndrome to advance existing diagnostic and therapeutic protocols. The therapy with Interferon-gamma (IFN-γ) and the use of S1P receptor modulators showed promising results. However, there are many unknowns about these mechanisms and possible novel therapies. Therefore, the inflammation and autoimmunity triggered by Covid-19 should be further investigated to improve existing diagnostic procedures and therapeutic protocols for Covid-19.

Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs.

Gut microbiota is known as unique collection of microorganisms (including bacteria, archaea, eukaryotes and viruses) that exist in a complex environment of the gut. Recently, this has become one of the most popular areas of research in medicine because this plays not only an important role in disease development, but gut microbiota also influences drug pharmacokinetics. These alterations in drug pharmacokinetic pathways and drug concentration in plasma and blood often lead to an increase in the incidence of toxicological events in patients. This review aims to present current knowledge of the most commonly used drugs in clinical practice and their dynamic interplay with the host's gut microbiota as well as the mechanisms underlying these metabolic processes and the consequent effect on their therapeutic efficacy and safety. These new findings set a foundation for the development of personalized treatments specific to each metabolism, maximizing drugs' therapeutic effects and minimizing the side effects because they are one of the major limiting factors in treating patients.

Bioinspired engineered nickel nanoparticles with multifunctional attributes for reproductive toxicity.

Nickel nanoparticles (Ni-NPs) have potential applications in high-tech sectors such as battery manufacturing, catalysis, nanotube printing and textile. Apart from their increasing utilisation in daily life, there are concerns about their hazardous nature as they are highly penetrable in biological systems. The carcinogenic and mutagenic ability of Ni-NPs is evident but the research gaps are still there concerning the safety evaluation of Ni-NPs regarding male reproductive ability. This controlled randomized research was planned to assess the male reproductive toxicity of Ni-NPs in Sprague Dawley rats. Ni-NPs of spherical shape and mean particle size of 56 nm were used in the study, characterized by SEM, EDS and XRD. The twenty-five healthy rats (200-220 g) were used for toxicity investigation of Ni-NPs and divided into five groups; negative control (0 Ni-NPs), placebo group (0.9% saline) and three Ni-NPs treated groups (@ 15, 30 and 45 mg/kg BW). The results of 14 days of intraperitoneal exposure to Ni-NPs revealed that a higher dose (45 mg/kg BW) of Ni-NPs caused a significant reduction in body weight, serum testosterone, daily sperm production while the testis index and Ni accumulation and histological changes (necrosis in basement membrane and seminiferous tubules, vacuole formation) in testicular tissues increased with increasing dose of Ni-NPs. It can be concluded from the study that Ni-NPs have potential reproductive toxicity. This study provided the baseline data of Ni-NPs toxicity for the male reproductive system and can be applied for risk assessment in Ni-NPs based products.

Functional bioinspired nanocomposites for anticancer activity with generation of reactive oxygen species.

Cancer is a debilitating and deadly disease caused by the uncontrolled growth of aberrant cell populations. This disease cannot always be controlled with traditional therapies and medicines. Different medicines are being used for this purpose, however these medicines have their side effects and are harmful to healthy cells. A better way to cure cancer disease is by limiting the agglomeration of cancer cells, minimizing their growth and their population by destroying these harmful cells. This could be achieved by controlling the function of mitochondria and DNA in cancer cells with the use of biocompatible materials with tuneable physical properties. Accordingly, research is ongoing as to the use of nanomaterials and nanotechnology in medicine. Zinc oxide semiconductor nanoparticles have displayed good anticancer behaviour. They have unique properties such as biocompatibility, good stability, and are environmentally friendly. Owing to these characteristics, they are focused on biological applications such as drug delivery and cancer therapy. In the present research work, zinc oxide, titanium dioxide nanoparticles and titanium oxide-zinc oxide nanocomposites were successfully trailed for anti-cancer activity. Pure zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO2 NPs) and their nanocomposites (TiO2+ZnO NPs) were prepared by the co-precipitation technique. The structural properties were investigated by X-ray diffraction, which confirmed the Wurtzite structure of pure ZnO NPs. The morphology of the NPs was checked by scanning electron microscopy. For incident light having a higher energy band gap of nanomaterials, the electrons are excited to the conduction band and these electrons generate reactive oxygen species (ROS). The efficacy of these nanomaterials was checked by exposing the NPs to the human liver cancer cell HepG2. The MTT assay describes anticancer activity via cell viability. The cell viability of composites was observed to be greater than pure ZnO NPs. Their results showed that the structure of ZnO NPs remains the same with composites of TiO2 NPs, but the band gap of the composite was intermediate for individual samples. It also showed that the anticancer activity of composites was also less than pure ZnO NPs which is due to the reduction of ROS generation. This is observed that nanocomposites of ZnO and TiO2 could be effective in the development of a treatment of human liver cancer cells.

Polyvinyl alcohol and aminated cellulose nanocrystal membranes with improved interfacial compatibility for environmental applications.

Biogas up-gradation is a useful method to control CO2 emission and enhance the green process. The demand for renewable sources is increasing due to the depletion of fossil fuels. Thin-film nanocomposites functionalized with tunable molecular-sieving nanomaterials have been employed to tailor membranes with enhanced permeability and selectivity. In this work, the cellulose nanocrystals as a filler in the polyvinyl alcohol matrix are prepared to achieve high-performance facilitated transport membranes for CO2 capture. Considering the mechanical stability, interfacial compatibility and high moisture uptake of the filler, the main objective of this work was to develop a novel aminated CNC (Am-CNC)/polyvinyl alcohol nanocomposite membrane for biogas upgrading. The hydroxyl groups (O-H) on the reducing end of the cellulose nanocrystals were replaced by amino groups (N-H2). It was discovered through Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) that adding Am-CNCs in PVA membranes shows an increment in the CO2 removal and effectively upgrades the biogas. The effect of change in concentration of Am-CNC and feed pressure was investigated. The results showed that with increasing Am-CNC concentration up to 1.5 wt%, the thickness of the selective membrane layer increased from 0.95 to 1.9 µm with a decrease in the moisture uptake from 85.04 to 58.84%. However, the best CO2 permeance and selectivity were achieved at 0.306 m3/m2.bar.h (STP) and 33.55, respectively. Furthermore, there was a more than two-fold decrease in CO2 permeance and a 27% decrease in the CO2/CH4 selectivity when the feed pressure increased from 5 to 15 bar. It was revealed that PVA/Am-CNC membrane is high performing for the biogas upgradation.

Cellulose acetate based sustainable nanostructured membranes for environmental remediation.

Membrane-based gas separation has a great potential for reducing environmentally hazardous carbon dioxide (CO2) gas. The polymeric membranes developed for CO2 capturing have some limitations in their selectivity and permeability. There is a need to overcome these issues and developed such membranes having high-performance CO2 capture with cost-effectiveness. The present study aimed to synthesize mixed matrix membranes (MMMs) having improved properties CO2 adsorption performance and stability than that of pure polymer. Further, the effect on CO2 adsorption by increasing the filler concentration in MMMs was investigated. The MMMs were synthesized by incorporating (1-5 wt%) Cu-MOF-GO composites as filler into cellulose-acetate (CA) polymer matrix by adopting the solution casting method. The performance of MMMs was studied by changing the Cu-MOF-GO composite concentration (1-5 wt%) in the polymer matrix at 45 °C up to 15 bar. Morphological analysis by using SEM confirms that by increasing the concentration of Cu-MOF-GO more than 3% will result in their agglomeration in MMM. The successful incorporation of MOF within the polymer matrix of MMMs was confirmed through the presence of functional groups using FTIR and Raman spectroscopy. XRD analysis revealed that pure CA changes its semi-crystalline behaviour into crystalline by the addition of Cu-MOF-GO. The maximum tensile stress and strain rate of MMMs was 45.1 N/mm2 and 12.8%. In addition, with an increase in (4-5 wt%) Cu-MOF-GO concentration the hydrophilicity of MMMs decreases. The maximum uptake rate of CO2 was 1.79 mmol/g and 7.98 wt% at 15 bar. The adsorption results conclude that Cu-MOF-GO composite and CA-based MMM can be effective for CO2 capture.