The Role of miRNAs in Dexmedetomidine's Neuroprotective Effects against Brain Disorders.

There are limited neuroprotective strategies for various central nervous system conditions in which fast and sustained management is essential. Neuroprotection-based therapeutics have become an intensively researched topic in the neuroscience field, with multiple novel promising agents, from natural products to mesenchymal stem cells, homing peptides, and nanoparticles-mediated agents, all aiming to significantly provide neuroprotection in experimental and clinical studies. Dexmedetomidine (DEX), an α2 agonist commonly used as an anesthetic adjuvant for sedation and as an opioid-sparing medication, stands out in this context due to its well-established neuroprotective effects. Emerging evidence from preclinical and clinical studies suggested that DEX could be used to protect against cerebral ischemia, traumatic brain injury (TBI), spinal cord injury, neurodegenerative diseases, and postoperative cognitive disorders. MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level, inhibiting the translation of mRNA into functional proteins. In vivo and in vitro studies deciphered brain-related miRNAs and dysregulated miRNA profiles after several brain disorders, including TBI, ischemic stroke, Alzheimer's disease, and multiple sclerosis, providing emerging new perspectives in neuroprotective therapy by modulating these miRNAs. Experimental studies revealed that some of the neuroprotective effects of DEX are mediated by various miRNAs, counteracting multiple mechanisms in several disease models, such as lipopolysaccharides induced neuroinflammation, ß-amyloid induced dysfunction, brain ischemic-reperfusion injury, and anesthesia-induced neurotoxicity models. This review aims to outline the neuroprotective mechanisms of DEX in brain disorders by modulating miRNAs. We address the neuroprotective effects of DEX by targeting miRNAs in modulating ischemic brain injury, ameliorating the neurotoxicity of anesthetics, reducing postoperative cognitive dysfunction, and improving the effects of neurodegenerative diseases.

Circulating MicroRNAs and Extracellular Vesicle-Derived MicroRNAs as Predictors of Functional Recovery in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.

Ferroptosis Involvement in Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors. Current standard therapy includes tumor resection surgery followed by radiotherapy and chemotherapy. Due to the tumors invasive nature, recurrences are almost a certainty, giving the patients after diagnosis only a 12-15 months average survival time. Therefore, there is a dire need of finding new therapies that could potentially improve patient outcomes. Ferroptosis is a newly described form of cell death with several implications in cancer, among which GBM. Agents that target different molecules involved in ferroptosis and that stimulate this process have been described as potentially adjuvant anti-cancer treatment options. In GBM, ferroptosis stimulation inhibits tumor growth, improves patient survival, and increases the efficacy of radiation and chemotherapy. This review provides an overview of the current knowledge regarding ferroptosis modulation in GBM.

Delta Variant in the COVID-19 Pandemic: A Comparative Study on Clinical Outcomes Based on Vaccination Status.

BACKGROUND: As the global battle against the COVID-19 pandemic endures, the spread of the Delta variant has introduced nuanced challenges, prompting a nuanced examination. MATERIALS AND METHODS: We performed a multilevel logistic regression analysis encompassing 197 patients, comprising 44 vaccinated individuals (V group) and 153 unvaccinated counterparts (UV). These patients, afflicted with the Delta variant of SARS-CoV-2, were hospitalized between October 2021 and February 2022 at the COVID-19 department of a University Centre in Cluj-Napoca, Romania. We compared patient characteristics, CT lung involvement, Padua score, oxygen saturation (O2 saturation), ventilation requirements, dynamics of arterial blood gas (ABG) parameters, ICU admission rates, and mortality rates between the two groups. RESULTS: The UV group exhibited a statistically significant (p < 0.05) proclivity toward developing a more severe form of infection, marked by elevated rates of lung involvement, oxygen requirement, ICU admission, and mortality. CONCLUSION: Our findings underscore the substantial efficacy of the vaccine in diminishing the incidence of severe disease, lowering the rates of ICU admissions, and mitigating mortality among hospitalized patients.

Nanotechnology Involved in Treating Urinary Tract Infections: An Overview.

Considered as the most frequent contaminations that do not require hospitalization, urinary tract infections (UTIs) are largely known to cause significant personal burdens on patients. Although UTIs overall are highly preventable health issues, the recourse to antibiotics as drug treatments for these infections is a worryingly spread approach that should be addressed and gradually overcome in a contemporary, modernized healthcare system. With a virtually alarming global rise of antibiotic resistance overall, nanotechnologies may prove to be the much-needed 'lifebuoy' that will eventually suppress this prejudicial phenomenon. This review aims to present the most promising, currently known nano-solutions, with glimpses on clinical and epidemiological aspects of the UTIs, prospective diagnostic instruments, and non-antibiotic treatments, all of these engulfed in a comprehensive overview.

miRNA Involvement in Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the RNA-induced silencing complex either degrade or prevent target messenger RNAs from being translated and thus, can modulate the synthesis of target proteins. In the neurological field, miRNAs have been evaluated as potential regulators in brain development processes and pathological events. Following ischemic hypoxic stress, the cellular and molecular events initiated dysregulate different miRNAs, responsible for long-terming progression and extension of neuronal damage. Because of their ability to regulate the synthesis of target proteins, miRNAs emerge as a possible therapeutic strategy in limiting the neuronal damage following a cerebral ischemic event. This review aims to summarize the recent literature evidence of the miRNAs involved in signaling and modulating cerebral ischemia-reperfusion injuries, thus pointing their potential in limiting neuronal damage and repair mechanisms. An in-depth overview of the molecular pathways involved in ischemia reperfusion injury and the involvement of specific miRNAs, could provide future perspectives in the development of neuroprotective agents targeting these specific miRNAs.

The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus.

Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.

Recovery following Orthognathic Surgery Procedures-A Pilot Study.

This study aims at evaluating and categorizing patients' objective and subjective postoperative recovery symptoms after bimaxillary orthognathic surgery assigning the healing process. The patients were monitored throughout the recovery process, and their symptoms were managed. A prospective, observational study was performed. Patients with Class II and III malocclusion (aged 18 to 35) were evaluated and monitored preoperatively, and postoperatively at 48 h, 2 weeks, 1 month, and 3 months postsurgery. A questionnaire was used to assess pain and anesthesia/hypoesthesia. The most common objective and subjective signs that were correlated with the healing process were edema, hematoma, trismus, pain, and anesthesia/hypoesthesia. Edema peaked at 48−72 h postoperatively (distance between eye's external canthus and gonion, mean difference = 4.53, between tragus and cheilion, mean difference = 7, between tragus and gnathion, mean difference = 4.65, p < 0.001); mouth opening amplitude was significantly decreased during the first two weeks postsurgery (class II, mean difference = 32.42, p = 0.006, class III, mean difference = 44.57, p < 0.001), but it steadily and considerably improved over three months. The nose tended to widen postsurgery. The most severe pain experienced by patients was of medium intensity in the mandibular body, described as pressure, and usually did not spread. Patients were most severely and persistently impacted by anesthesia/hypoesthesia.

The Role of Probiotic Bacillus Spores and Amino Acids with Immunoglobulins on a Rat Enteropathy Model.

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs due to their anti-inflammatory, analgesic and antipyretic pharmacological effects. Gastrointestinal side effects are some of the most severe and frequent side effects of NSAIDs. These depend on the balance of the gut microbiome, the abundance of Gram-negative bacteria, and the amount of lipopolysaccharide released. Therefore, restoring or improving gut bacteria balance with probiotic supplements could prove to be an adjuvant therapy against mild NSAID-induced enteropathy. Twenty-five Wistar albino male rats were divided into five groups. The negative control group was administered carboxymethylcellulose and the positive control group diclofenac (DIC), 8 mg/kg for 7 days, which represented the enteropathy model. Treatment groups consisted of a combination of pro-biotic spores (MSB), amino acids and immunoglobulins supplement (MM), which were also administered for 7 days. We analyzed hepatic injury markers (AST, ALT) and creatinine, and inflammatory markers, IL-6, TNF-α, PGE2, iNOS, as well as total antioxidant capacity. The results obtained in the present study suggest that the modulation of the intestinal microbiota by administration of probiotics (Bacillus spores), alone or in combination with immunoglobulins and amino acids, represents an attractive therapy for the prevention of NSAID-induced enteropathy.

Overview of the microbiota in the gut-liver axis in viral B and C hepatitis.

Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of 'protective' gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.

Endoscopic Ultrasound Elastography in the Assessment of Rectal Tumors: How Well Does It Work in Clinical Practice?

Endorectal ultrasound applications in the evaluation of rectal tumors could be a useful tool in achieving proper staging of rectal cancer. The purpose of this study was to compare the efficacy of rectal tumor staging by flexible endoscopic ultrasound (EUS) with real-time elastography (RTE) using the gold standard post-surgery histological analysis of the resected tissue as the control. The second aim of our research was to establish cutoff values for the EUS-RTE strain ratio corresponding to stages by independently comparing the stiffness values obtained with histology and EUS-RTE staging in order to minimize observation bias. We evaluated the records of 130 patients with a rectal tumor confirmed by biopsy. EUS was used in 70 patients, EUS-RTE-in the other 60. We found no statistically significant differences in staging accuracy when comparing EUS to EUS-RTE. Through a correspondence method between staging assessment and the EUS-RTE stain ratio, we identified cutoff intervals for T2, T3, and T4 staging that were nonoverlapping and proved to be statistically significant in terms of EUS-RTE values (significantly different ascending values from one interval to the other). We found that EUS-RTE offers slightly better, although not statistically significant sensitivity and specificity for T and N stage predictions compared to 2D EUS. Our results showed that EUS-RTE offers slightly higher sensitivity and specificity compared to EUS. Reliable cutoff intervals were found for strain rate elastography, previously available only for shear wave elastography (SWE) which is currently unavailable on any EUS system. Thus, these commonly available EUS-RTE systems can serve as a complementary tool in the staging of rectal tumors.

An Overview on the Mechanisms of Neuroprotection and Neurotoxicity of Isoflurane and Sevoflurane in Experimental Studies.

Since their first use, anaesthetic agents have seen major advancements and are now an indispensable element of surgical procedures. Two of the most used volatile anaesthetics are isoflurane and sevoflurane. These have neuroprotective effects on adult brains in different brain disorders, ranging from traumatic to hypoxic or ischemia-reperfusion injuries. In new-borns and elderly patients these effects are reversed, and volatile anaesthetics might have a neurotoxic effect, affecting the recovery and neurological capabilities of these patients. Since we are still using volatile anaesthetics, it is important to know in which conditions these substances are neurotoxic and neuroprotective, as well as to better understand the mechanisms underlying these effects. In this review we aim to summarise the current knowledge on the mechanisms involved in neuroprotection and neurotoxicity of neonatal, adult and aged brains and how these vary based on the brains age and underlying pathologies. This review should guide future experimental research towards less studied mechanisms and should help the development of neuroprotective strategies. Also, we provide a short summary of the substances used in experimental studies to prevent the neurotoxic effect of isoflurane and sevoflurane.

Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins Exert Protective Effects on a Rat Model of Ulcerative Colitis.

In inflammatory bowel disease (IBD), experimental models have proven to be important tools for evaluating potential therapeutic agents and for investigating the mechanisms of pathogenesis. Oxidative stress and the immune response have been associated with acetic acid (AA)-induced ulcerative colitis (UC). Our study aimed to evaluate, for the first time, the ability of a spore-based probiotic and an amino acid and immunoglobulin supplement in reducing tissue damage and inflammatory responses in an experimental animal model of UC. Forty-two Wistar rats were divided into six groups, receiving 1% carboxymethylcellulose, 4% AA, MegaSporeBiotic™ (MSB; 1 × 109 colony forming units/day) and MegaMucosa™ (MM; 70 mg/100 g/day). Pretreatment with MSB or MM alone and in combination significantly lowered inflammation and reduced damage to the colonic mucosa. Pretreatment with these agents resulted in levels of proinflammatory cytokines, vascular tight junction proteins, and measures of oxidative stress similar to those reported for methylprednisolone, one of the first-line therapies for moderate to severe activity of UC. The protection was further confirmed by histologic analysis of the colon tissue. In conclusion, pretreatment with probiotic spore-forming Bacillus strains and a supplement of amino acids in combination with immunoglobulins exhibited anti-inflammatory and antioxidant effects in an AA-induced rat model of UC.

Targeting Oxidative Stress Reduction and Inhibition of HDAC1, MECP2, and NF-kB Pathways in Rats With Experimentally Induced Hyperglycemia by Administration of Thymus marshallianus Willd. Extracts.

The effects of two lyophilized extracts obtained from the aerial parts of Thymus marschallianus Willd. and harvested from wild flora (TMW) and obtained from culture (TMC) were evaluated in Wistar rats with experimentally induced hyperglycemia. The hyperglycemia was induced by streptozotocin (STZ) administration and the obtained results were evaluated in comparison for TMW and TMC. The polyphenolic composition of extracts was evaluated by spectrophotometrical and LC-MS methods. In vitro antioxidant capacity assays (DPPH, FRAP, EPR) were performed in order to preliminary establish the ability of tested samples to protect against free radical induced damage. Afterwards, the effects of these extracts were assessed in vivo on rats with experimental-induced hyperglycemia. Oxidative stress biomarkers (e.g. malondialdehyde-MDA), phosphorylated transcription factor subunit of nuclear kappaB (NF-kB) p65, methyl CpG binding protein (MECP) 2 and histone deacetylase 1 (HDAC1) expressions in hippocampus and frontal lobe were assessed. Open Field Test (OFT) and Elevated Plus Maze (EPM) were conducted on tested animals. Malondialdehyde (MDA) levels and HDAC1and MeCP2 expressions increased significantly in hippocampus (p<0.05) and frontal lobe (p<0.001) of diabetes group compared to the control group in parallel with decreasing of GSH/GSSG ratio. TMW and TMC administration reduced blood glucose levels and diminished lipid peroxidation, HDAC1 expression and enhanced antioxidant capacity in frontal lobe. TMW improved central locomotion of rats, increased phospho-NFkB p65 and diminished MECP2 expressions in hippocampus. Both tested samples exerted a beneficial effect by increasing the antioxidant defense. Our findings indicate that the administration of these extracts might represent a good option in the treatment of diabetes and its complications.

Acute Intermittent Porphyria - an Unexpected Association in a Patient with Newly Diagnosed Crohn's Disease.

The association of Crohn's disease (CD) with acute intermittent porphyria (AIP), both without a family or personal pathological history, is a very rare clinical possibility. We present the case of a 23-year-old male diagnosed on the same admission with ileal CD and with an AIP crisis. The diagnosis was challenging as the symptoms overlapped. Crohn's disease was complicated with intestinal occlusion and sepsis; the inflammatory, metabolic and septic changes represented the trigger factor for the first AIP seizure. The neurological symptoms were the key element for AIP diagnosis. The presence of atypical extra-intestinal manifestations in CD patients should raise also the possibility of AIP.

Microbiota and Immune-Mediated Skin Diseases-An Overview.

In recent years, increased attention has been paid to the relationship between microbiota and various diseases, especially immune-mediated diseases. Because conventional therapy for many autoimmune diseases is limited both in efficacy and safety, there is an increased interest in identifying nutraceuticals, particularly probiotics, able to modulate the microbiota and ameliorate these diseases. In this review, we analyzed the research focused on the role of gut microbiota and skin in immunity, their role in immune-mediated skin diseases (IMSDs), and the beneficial effect of probiotics in patients with this pathology. We selected articles published between 2009 and 2019 in PubMed and ScienceDirect that provided information regarding microbiota, IMSDs and the role of probiotics in these diseases. We included results from different types of studies including observational and interventional clinical trials or in vivo and in vitro experimental studies. Our results showed that probiotics have a beneficial effect in changing the microbiota of patients with IMSDs; they also influence disease progression. Further studies are needed to better understand the impact of new therapies on intestinal microbiota. It is also important to determine whether the microbiota of patients with autoimmune diseases can be manipulated in order to restore homeostasis of the microbiota.

Paradoxical Effect of Grape Pomace Extract on Cisplatin-Induced Acute Kidney Injury in Rats.

Cisplatin is one of the most used drugs in the therapy of different types of cancer. However, its use is limited by nephrotoxicity. This study investigated the effects of a commercially available grape pomace extract (GE) from Vitis vinifera on cisplatin-induced kidney toxicity in rats. Sixty-four male Wistar albino rats were randomly divided into eight groups. Groups 1-3 were controls, receiving 0.9% saline and doses 1 and 2 of GE respectively. Cisplatin was given to groups 4-8. Two groups received pretreatment with GE, while another two groups received pre- and post-treatment with GE. Blood samples were collected and all animals sacrificed. Kidneys were harvested for histopathological analysis. GE significantly increased blood creatinine and urea levels, the severity of kidney histopathological damage, and mortality in all cisplatin groups, except for group 7 which received pre- and post-treatment with a low dose of GE. Renal toxicity was determined by mortality and severe histopathological renal lesions. Additionally, the serum total antioxidant capacity (TAC) was not significantly modified in the treated groups compared to the control. These results indicate that the GE did not have a protective effect on cisplatin-induced nephrotoxicity; on the contrary, GE accentuated the toxic effect of cisplatin.

The role of p-Stat3 Y705 immunohistochemistry in glioblastoma prognosis.

BACKGROUND: In spite of the multimodal treatment used today, glioblastoma is still the most aggressive and lethal cerebral tumour. To increase survival in these patients, novel therapeutic targets must be discovered. Signal transducer and activator of transcription 3 (Stat3), a transcription factor that controls normal cell differentiation and survival is also involved in neoplastic celltransformation. In this study we evaluated the immunohistochemical expression of pY705-Stat3 in patients with primary glioblastoma and determined its prognostic role by correlating it with survival. METHODS: This retrospective study included 94 patients diagnosed with glioblastoma. We determined the localization, number of positive cells, and marker intensity for pY705-Stat3 in these patients with the use of immunohistochemistry. The prognostic role was determined by correlating pY705-Stat3 expression on formalin-fixed paraffin-embedded tumour tissues with the patient's survival in univariate and multivariate COX regressions. RESULTS: We found a statistically significant difference in survival between the patients with more than 20% pY705-Stat3 positive cells and those with less than 20% pY705-Stat3 positive cells (8.9 months median survival versus 13.7 months medial survival, p <  0.001). On multivariate analyses with the COX proportional hazards regression model including pY705-Stat3 expression, age and relapse status, pY705-Stat3 status was an independent prognostic factor in glioblastoma (P <  0.001). CONCLUSION: The results obtained show that the immunohistochemical expression of pY705-Stat3 correlates with survival in glioblastoma. This study identifies Stat3 as a possible target for existing or new developed Stat3 inhibitors.