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Abstract Background Mineralocorticoid receptor antagonists (MRAs) have been shown to improve outcomes in various populations of heart failure (HF) patients. However, the impact of concomitant diseases, such as diabetes mellitus (DM), on these outcomes remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of MRAs in heart failure patients with and without diabetes mellitus. Methods A systematic search was conducted on PubMed, Scopus, and Google Scholar databases up to April 30, 2024. Data analysis was performed using a random-effects model to account for variability across studies, and statistical analysis was carried out using Review Manager 5.4. Efficacy and safety parameters were evaluated in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Results The meta-analysis included a total of 21,832 subjects from ten studies. The pooled results demonstrated that MRAs, compared to placebo, significantly reduced all-cause mortality in HF patients with and without DM (RR: 0.85; 95%CI 0.75–0.96; p = 0.009). A similar effect was observed in HF patients without DM (RR: 0.83; 95%CI 0.71–0.97; p = 0.02), while no significant effect was detected in the DM subgroup (RR: 0.87; 95%CI 0.69–1.11; p = 0.27). Both treatments had comparable effects on cardiovascular mortality in HF patients with and without DM (RR: 0.88; 95%CI 0.82–0.94; p = 0.0002), in HF patients with DM (RR: 0.90; 95%CI 0.81–1.01; p = 0.08), and in the non-DM subgroup (RR: 0.86; 95%CI 0.79–0.94; p = 0.0009). MRAs significantly reduced the risk of cardiovascular mortality in HF patients with and without DM (RR: 0.82; 95%CI 0.72–0.94; p = 0.005) and in HF patients with DM (RR: 0.79; 95%CI 0.63–0.98; p = 0.03), but no significant effect was observed in the non-DM subgroup (RR: 0.85; 95%CI 0.69–1.05; p = 0.13). Furthermore, compared to placebo, MRAs were associated with an increased risk of hyperkalemia (> 5.5 mEq/L) in HF patients with and without DM (RR: 1.63; 95%CI 1.18–2.24; p = 0.003), particularly in HF patients with DM (RR: 1.44; 95%CI 0.97–2.13; p = 0.07) and in the non-DM subgroup (RR: 1.87; 95%CI 1.34–2.61; p = 0.0002). Conclusion MRAs are effective in reducing all-cause mortality, cardiovascular death, and cardiovascular mortality in heart failure patients. However, the use of MRAs is associated with an increased risk of hyperkalemia, necessitating careful monitoring, particularly in patients with diabetes mellitus.

Abstract Background The beta-blocker (BB) initiation in acute heart failure (AHF) patients is still controversial. Some show the benefit of BB employment in decreasing the mortality outcome. This study aims to assess the safety and efficacy of in-hospital and long-term outcomes of BB initiation in AHF hospitalized patients. We searched multiple databases examining the outcome of AHF patients who had administered BB as the therapy initiation. Primary outcomes were all-cause mortality, composite endpoint after BB initiation when hospitalized, and post-discharge all-cause mortality. The secondary outcomes were adverse events after in-hospital BB initiation, including hypotension and symptomatic bradycardia after BB initiation when hospitalization and rehospitalization. Results Eight cohort studies with 16,639 patients suffering from AHF and cardiogenic shock, with 9923 participants allocated to the early BB group and 6,713 patients in the control group. The follow-up durations ranged from 2 to 24 months. Early BB administration significantly reduced in-hospital composite endpoints (RR: 0.42; 95% CI (0.30–0.58); p

Abstract Background Echocardiographic prognostic indicators of precapillary pulmonary hypertension (PH) mortality has been inconclusive. This study aims to examine the prognostic values of right ventricular echocardiographic functional parameters in predicting precapillary PH mortality. Methods Systematic searches were conducted in the ScienceDirect, Medline, and Cochrane databases for longitudinal studies. Assessments included means and hazard ratios (HRs) for Tricuspid Annular Plane Systolic Excursion (TAPSE), Right Ventricular Systolic Pressure (RVSP), Right Ventricular Longitudinal Strain (RVLS), Right Ventricular Fractional Area Change (RVFAC), Right Ventricular Ejection Fraction (RVEF), and Right Ventricular Index of Myocardial Performance (RIMP). Results The meta-analysis included 24 cohort studies comprising 2171 participants. Mean values were as follows: TAPSE 17.62 mm, RVSP 77.50 mmHg, RVLS − 16.78%, RVFAC 29.81%, RVEF 37.56%, and RIMP 0.52. TAPSE (HR: 1.28; 95% CI 1.17–1.40; p

Abstract Background Atrial fibrillation (AF) poses a significant stroke risk in heart disease patients. This systematic review aims to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) versus vitamin K antagonists (VKAs) in AF patients with and without any valvular heart disease (VHD/N-VHD). Methods A systematic search was conducted on PubMed, Scopus, and Google Scholar up to March 3, 2022. Efficacy and safety parameters were analyzed. Results A total of 85,423 subjects from 10 studies were included in this meta-analysis. NOACs and VKAs showed similar effects on ischemic stroke in AF patients with VHD/N-VHD (RR 0.97; 95% CI 0.72–1.30; p = 0.83) and also on systemic embolic events (RR 1.02; 95% CI 0.83–1.25; p = 0.86). Similar effects were seen in VHD and N-VHD subgroups. Both treatments had similar effects on myocardial infarction in AF patients with VHD/N-VHD (RR 0.79; 95% CI 0.49–1.26; p = 0.32), VHD (RR 0.78; 95% CI 0.59–1.02; p = 0.07), and N-VHD subgroups (RR 0.82; 95% CI 0.30–2.21; p = 0.69). NOACs reduced the risk of intracranial bleeding in AF VHD/N-VHD (RR 0.64; 95% CI 0.54–0.77; p

Background: The geographical diversity and clinical presentation differences of acute coronary syndrome (ACS) patients in Bali significantly influence the management performance and intervention outcomes. Bali, an island with varied geography, presents unique challenges for timely access to percutaneous coronary intervention (PCI) facilities, which are concentrated in South Bali. This study aims to describe annually the clinical characteristics of ACS patients in Bali, focusing on geographical factors and management performance. Methods: The regional data from the Indonesia Acute Coronary Syndrome Registry (One ACS) were utilized in this study. The study population consisted of patients aged over 18 years who were treated for ACS from 2017 to 2023 at Prof. Dr. I.G.N.G Ngoerah Central General Hospital in Denpasar, Bali. Several outcomes were described, including baseline characteristics, transfer time, door-to-balloon time (DTB), door-to-wire time (DTW), ambulance transport time, patient transport time, and major adverse cardiac event (MACE) outcomes. Results: A total of 4588 ACS patients based in Bali were included from 2017 to 2023. The majority of ACS patients originated from Denpasar city (44.1 %), followed by Badung (19.2 %) and Gianyar (8.5 %). More than half of the patients (57.9 %) were referred from primary healthcare, with a mean transfer time of 247.45 ± 698.26 min. Mortality rates were high, with significant numbers of cardiac arrests, heart failure, and cardiogenic shock. On multivariate analysis, shortness of breath, chest pain during light activity, patients seeking first medical contact (FMC) in Karangasem, and self-admission to the hospital were independently associated with mortality. Conclusions: The geographical challenges of Bali, particularly the limited distribution of PCI-capable facilities, contribute to delays in treatment and varied outcomes for ACS patients. Improvements in healthcare systems across Bali are required to conform with current guidelines and enhance intervention outcomes.

The current gold-standard management of hyperglycemia in individuals with type 1 diabetes mellitus (T1DM) is insulin therapy. However, this therapy is associated with a high incidence of complications, and delaying the onset of this disease produces a substantially positive impact on quality of life for individuals with a predisposition to T1DM, especially children. This review aimed to assess the use of gamma-aminobutyric acid (GABA) to delay the onset of T1DM in children. GABA produces protective and proliferative effects in 2 ways, β cell and immune cell modulation. Various in vitro and in vivo studies have shown that GABA induces proliferation of β cells, increases insulin levels, inhibits β-cell apoptosis, and suppresses T helper 1 cell activity against islet antigens. Oral GABA is safe as no serious adverse effects were reported in any of the studies included in this review. These findings demonstrate promising results for the use of GABA treatment to delay T1DM, specifically in genetically predisposed children, through immunoregulatory effects and the ability to induce β-cell proliferation.

Abstract Background Epilepsy initiation involves multifactorial etiologies, including genetic susceptibility, structural anomalies, and glial cell dysregulations, particularly in astrocytes. Despite advancements in understanding various factors, the mechanisms of astrocyte dysregulation in epilepsy, critical for neural homeostasis, remain elusive, requiring comprehensive evaluation of molecular pathways and cellular interactions for future targeted interventions. Methods A systematic search of PubMed, ScienceDirect, and the Cochrane databases up to January 1st 2024 identified relevant studies predominantly from experimental models, forming the basis for an in-depth analysis of astrocytic contributions to epileptic pathophysiology. The aims, subjects, epilepsy induction techniques, assessment methods, and findings of each studies were presented. Results A total of 24 clinical trials met the inclusion criteria and were included in the systematic review. Altered potassium buffering compromises extracellular potassium regulation, fostering hyperexcitability. Aquaporin dysfunction disrupts water homeostasis, aggravating seizure susceptibility. Disturbances in glutamatergic transmission, marked by changes in glutamate transporter function, contribute to excitotoxicity, fueling epileptogenesis. Intricacies in calcium signaling and disruptions in calcium-binding proteins tip intracellular calcium balance towards hyperexcitability. Dysfunctional GABA transporters compromise inhibitory neurotransmission, upsetting excitatory–inhibitory balance. Gap junction protein dysregulation disrupts astroglial networks, impacting neuronal synchronization in epileptogenic circuitry. Compromised BBB allows entry of epileptogenic factors, exacerbating the epileptogenic milieu. Conclusions Collectively, these astrocytic dysregulations unveil intricate contributors to epilepsy onset and progression.

Abstract Background Alzheimer’s disease (AD) stands as a formidable challenge within the realm of neurodegenerative disorders, characterized by its inexorable progression and the profound cognitive impairments it engenders. Despite decades of research, the management of AD remains in a conundrum, with currently available treatments offering only modest symptomatic relief and none that can definitively alter the course of the disease. Objective This investigation seeks to provide a concise overview of the influence of probiotics on the cognitive aspects of AD, drawing upon a compilation of conducted studies. Methods The study was conducted by means of comprehensive searches in MEDLINE, Pubmed, and Google Scholar databases spanning from January 2015 to December 2020. The composition of this review adhered to the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The evaluation of eligibility criteria was guided by the Population, Intervention, Comparator, Outcome, and Study Design (PICOS) framework, a methodology that was systematically applied to each identified research entry. Results Upon the implementation of the search protocol, a total of five articles that satisfied the predetermined inclusion criteria were incorporated into this review. Among these, four encompassed randomized controlled trials (RCTs), while the fifth pertained to an explorative interventional study. AD stands as a progressive neurodegenerative affliction of considerable clinical import. Through the assessment of diverse investigations, compelling evidence has emerged affirming that probiotic microorganisms, acting via the intricate gut–brain axis signaling pathway, harbor the capacity to ameliorate cognitive function in AD. The collective findings across all the studies unequivocally indicate a notable enhancement in cognitive function subsequent to the administration of probiotic supplementation (p

Abstract Background The impacts of single high-dose statin preloading in patients undergoing percutaneous coronary intervention (PCI) have not been fully examined. This study aims to evaluate post-procedure impacts of single high-dose statin pretreatment with acute coronary syndrome (ACS). Methods The meta-analysis reviewed Cochrane, PubMed, and Medline databases for studies comparing single high-dose atorvastatin or rosuvastatin to placebo in ACS patients undergoing PCI. The primary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, and target vessel revascularization (TVR) at three months. Secondary endpoints examined were the TIMI flow grade 3 and left ventricular ejection fraction (LVEF). Results Comprehensive analysis was conducted on fifteen RCTs, encompassing a total of 6,207 patients (3090 vs 3117 patients). The pooled results demonstrated that a single high-dose of statin administered prior to PCI led to a significant decrease in the incidence of MACE at three months post-PCI compared to the control group (OR 0.50, 95%CI 0.35–0.71, p = 0.0001). The occurrence of MI (OR 0.57, 95%CI 0.42–0.77, p = 0.0002), all-cause mortality (OR 0.56, 95%CI 0.39–0.81, p = 0.0002), and TVR (OR 0.56, 95%CI 0.35–0.92, p = 0.02) was significantly lower in the statin single high-dose group compared to the control group. No significant effects on TIMI flow grade 3 (OR 1.20, 95%CI 0.94–1.53, p = 0.14) or left ventricular ejection fraction (OR 2.19, 95%CI − 0.97 to 5.34, p = 0.17) were observed. Subgroup analysis demonstrated reduced incidence of MACE with a single dose of 80 mg atorvastatin (OR 0.66, 95%CI 0.54–0.81, p

Objective: Morbus Hansen (MH), caused by Mycobacterium leprae, is marked by neuropathic pain. Prior studies link low vitamin D levels to diabetic neuropathic pain, yet research on its role in MH-related neuropathic pain is limited. This study investigates the role of vitamin D deficiency in MH-related neuropathic pain. Materials and Methods: An analytical cross-sectional study was conducted among multibacillary (MB) MH patients at Prof. Dr. I.G.N.G. Ngoerah Hospital, Bali from April to August 2023. Neuropathic pain was assessed using the Douleur Neuropathique 4 (DN4) questionnaire, while serum 25(OH)D levels determined vitamin D status. The cutoff for deficiency was determined via ROC curve analysis. Results: Among 42 participants, those without neuropathic pain exhibited higher mean serum vitamin D levels than those with neuropathic pain (28.69 ± 8.16 vs. 22.11 ± 9.54 ng/ml; p=0.021). The ROC curve identified a cutoff value of 30.25 ng/ml, categorizing participants into vitamin D deficiency (

Abstract Background Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through ablation. This meta‐analysis evaluated the outcomes of catheter ablation (CA) in different types of IPAS based on procedural guidance and location. Methods A systematic search was conducted across multiple databases to identify studies reporting on ventricular arrhythmia (VA) events before and after CA in IPAS, including BrS, Long‐QT syndrome (LQTS), Early repolarization syndrome (ERS), and Idiopathic ventricular fibrillation (IVF). The primary outcomes were VA recurrence and VA burden, evaluated through conditional subgroup analysis. Procedural data were collected as secondary outcomes. Results A total of 21 studies involving 584 IPAS patients who underwent CA were included. Following a mean follow‐up duration of 33.5 months, substrate‐based ablation demonstrated efficacy in reducing VA recurrence across all types of IPAS [RR 0.23; 95% CI (0.13–0.39); p

Background: Ejection fraction (EF) is often used as a prognostic indicator and for classifying heart failure (HF) patients. This study evaluates the association of echocardiographic parameters with HF with improved EF (HFimpEF). Methods: This single-centre study retrospectively included patients with HF with reduced EF (HFrEF) from a cohort of admitted patients over 2018-2020, who were then followed up prospectively until 2023. The control group was categorized as patients with non-recovered HFrEF, and the population group was categorized as patients with HFimpEF. Results: A total of 176 patients with HFrEF were included in the study. Non-ischemic etiology was found to be the most prevalent cause of HFimpEF. The baseline echocardiography examination revealed that the HFimpEF group exhibited significantly higher values for tricuspid annular plane systolic excursion (TAPSE; P < 0.001) and inferior vena cava diameter (P < 0.001). The non-recovered HFrEF group demonstrated higher baseline left atrial volume index (LAVi) values (P < 0.001). In multivariate analysis, a higher value of TAPSE (odds ratio 3.071; P = 0.008) and a lower value of LAVi (odds ratio 2.034; P = 0.008) were independent echocardiography variables associated with HFimpEF. After a mean follow-up duration of 32.5 ± 9.1 months, the HFimpEF group had higher survival from rehospitalization due to worsening HF and lower all-cause mortality (log rank P < 0.001 and P = 0.005, respectively). Conclusions: Higher TAPSE and lower LAVi in baseline were associated with the transition from HFrEF to HFimpEF. The HFimpEF group had better survival compared to those with non-recovered HFrEF. Résumé: Contexte: La fraction d’éjection est souvent utilisée comme indicateur pronostique et comme élément de classification des patients atteints d’insuffisance cardiaque. La présente étude visait à évaluer l’association entre les paramètres échocardiographiques et l’insuffisance cardiaque avec fraction d’éjection améliorée (ICFEA). Méthodologie: Cette étude monocentrique a été menée de façon rétrospective auprès d’une cohorte de patients atteints d’insuffisance cardiaque avec fraction d’éjection réduite (ICFER) traités entre 2018 et 2020, et cette cohorte a été suivie de façon prospective jusqu’en 2023. Les patients du groupe témoin ont été classés comme ayant une ICFER ne s’étant pas résorbée, et les patients de la population étudiée ont été classés comme ayant une ICFEA. Résultats: Au total, 176 patients présentant une ICFER ont été inclus dans l’étude. La cause la plus fréquente d’ICFER était une étiologie non ischémique. Lors de l’évaluation échocardiographique initiale, les patients du groupe ayant progressé vers l’ICFEA présentaient des valeurs significativement plus élevées en ce qui concerne l’excursion systolique du plan de l’anneau tricuspide (TAPSE pour tricuspid annular plane systolic excursion) (p < 0,001) et le diamètre de la veine cave inférieure (VCI) (p < 0,001). D’autre part, les patients du groupe dont l’ICFER ne s’est pas résorbée présentaient des valeurs initiales plus élevées à l’indice de volume auriculaire gauche (IVAG) (p < 0,001). Lors d’une analyse multivariée, des valeurs de TAPSE plus élevées (rapport de cotes [RC] de 3,071; p = 0,008) et des valeurs plus faibles d’IVAG (RC de 2,034; p = 0,008) étaient deux variables échocardiographiques indépendantes associées avec la progression vers l’ICFEA. Après un suivi d’une durée moyenne de 32,5 ± 9,1 mois, le groupe présentant une ICFEA présentait un taux plus élevé de survie sans réhospitalisation due à une aggravation de l’IC et un taux plus faible de mortalités toutes causes confondues que le groupe dont l’ICFER ne s’était pas résorbée (p selon le test logarithmique par rangs < 0,001 et p = 0,005, respectivement). Conclusions: Une valeur de TAPSE élevée et un IVAG faible à l'évaluation initiale étaient associés à un passage de l’ICFER à l’ICFEA. La survie de patients présentant une ICFEA était supérieure à celle des patients présentant une ICFER non résorbée.

Abstract Background Anti-N-methyl d-aspartate (NMDA) receptor encephalitis is an autoimmune encephalitis characterized by neuronal surface antibodies targeting NMDA receptor in the spinal fluid and serum. After acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis is the most frequent cause of autoimmune encephalitis. Despite its clinical significance, the exact prevalence and optimal treatment strategies for this condition remain poorly understood. This comprehensive review aims to evaluate the therapeutic potential of bortezomib as a novel therapy for anti-NMDA receptor encephalitis in hopes of mitigating symptoms and improving outcomes for anti-NMDA receptor encephalitis patients. Results The disease is primarily triggered by immunoreactivity against the NMDA receptor 1 (NR1). Recurrence rates are of significant concern in the treatment of anti-NMDA receptor encephalitis, given that a substantial portion of patients are unresponsive to immunosuppressive and immunomodulatory therapies. Thus, the exploration of alternative therapies is necessary. In recent years, bortezomib, a proteasome inhibitor, has emerged as a potential therapeutic candidate by inhibiting autoantibody production against NMDA receptor. Bortezomib exerts immunosuppressive and immunomodulatory effects by inhibiting the production of autoantibodies against NMDA receptor. Studies suggest that bortezomib, by inhibiting proteasome activity and altering antigen presentation, can suppress autoantibody production and immune cell activation, contributing to clinical improvement. However, literature reviews on the utilization of bortezomib in the context of anti-NMDA receptor encephalitis are still highly limited. Conclusions Bortezomib presents a promising avenue for intervention. While initial studies suggest its potential to modify the immune response and alleviate symptoms, further comprehensive investigations are imperative to establish optimal dosing, usage guidelines, and long-term safety profiles.

Abstract Alzheimer’s disease (AD) is a form of dementia marked by the accumulation of neuritic plaques and neurofibrillary tangles through the action of GSK-3β with both significant epidemiological and clinical impact. Current pharmacological treatment approaches are focused on symptomatic relief and aims to suppress AD’s progression rather than disease modification. This issue has triggered further investigations about tau pathology as an important component in AD’s pathophysiology, one of them being the Akt signaling pathway. Based on the problem served by AD, combined with the non-existence of conclusive therapy for this disease; hence, this study strives to further investigate the potential therapeutical benefit of Akt signaling towards AD. A total of 82 studies are included, consisting of both national and international articles creating a narrative review based on the PRISMA checklist. Variables searched on this study, include Alzheimer’s disease (AD), Akt signaling, serine-9 phosphorylation, and GSK-3β. Tau protein accumulation has been a mainstay in the physiopathology of AD, which are largely influenced by the GSK-3β expression. Akt signaling has been shown to inactivate GSK-3β through serine-9 phosphorylation. Thus, modulating and optimizing the Akt signaling pathway present encouraging prospects for the development of innovative and efficacious therapeutic strategies in addressing AD. Several studies have tried to estimate the harm and benefit as well as dose–effect relationship between Akt signaling and AD, concluding a promising beneficial effect for AD therapy. Here, we show the beneficial therapeutic effects of Akt signaling towards AD through both theoretical and empirical standpoints.

Abstract Background Ruptured sinus of Valsalva aneurysm (RSoVA) is an uncommon cardiac anomaly that may occasionally coexist with additional congenital heart disease (CHD). The presence of such congenital cardiac anomalies, frequently involving a ventricular septal defect (VSD), is of significant clinical importance and warrants vigilant detection during echocardiographic assessments to prevent oversight. Case presentation Three cases of RSoVA accompanied by VSD are presented in which all patients manifested symptoms of shortness of breath (SOB). In the first patient, right and left heart catheterization was undertaken; however, the images failed to reveal any evidence of VSD flow due to the occlusion of a small VSD by the prolapsed right coronary cusp (RCC). Prior to surgical intervention, multimodal imaging was conducted, revealing the presence of RSoVA extending into the right ventricle (RV) along with the VSD. The second patient had a prior childhood diagnosis of VSD but had not undergone further medical intervention. Transoesophageal echocardiography (TEE) was subsequently performed, identifying the presence of RSoVA, a small VSD, and valvular heart disease. The third patient presented with heart failure, exacerbated during her second pregnancy. TEE was also administered to this patient, revealing the presence of RSoVA accompanied by a small subaortic VSD with a left-to-right shunt. All three patients were scheduled for surgical repair of the ruptured sinus of Valsalva and closure of the VSD. Conclusions The coexistence of RSoVA and CHD, typically VSD, is frequently observed in patients experiencing symptoms of SOB. Recognizing the presence of CHD in individuals with RSoVA is of paramount importance, as it can significantly influence their medical management and treatment strategies.

Hepatitis B is caused by a hepatitis B virus infection, causing inflammation of the liver. The therapeutic approach used to help treat HBV infection has been based on re-establishing a functioning T cell response and limiting additional negative consequences. Due to inadequate outcomes, new strategies for enhancing the immune response and inducing a particular HBV immune response have been developed. Activation of toll-like receptor 7 plays a role in mediating the immune response. TLR7 has shown to increase T cell activity, increase production of cytokines, increase the number of NK cells and lower serum concentrations of HBsAg, thus showing high potential to prevent and treat chronic hepatitis B. Evaluation of NK cell cytokine generation and degranu-lation reveals a considerable improvement in every cell function when compared to baseline values. However, TLR agonists are microscopic molecules that are rapidly eliminated from the system following ingestion and may cause significant systemic adverse effects. Poly(Ethylene Glycol)-Poly(Lactic Acid) can be utilised to increase the effectiveness of the toll-like receptor 7 agonist and lower the negative effects of the TLR7 agonist. TLR7 agonist distribution may be enhanced by an effective drug carrier, and conjugating a macromolecule may increase pharmacokinetics without toxicity or other negative side effects. The Poly(Ethylene Glycol)-Poly(Lactic Acid) TLR 7 agonist is potentially beneficial in treating hepatitis B as an immune response stimulant.

Abstract Multi-infarct dementia (MID) is described as a chronic progressive decline in cortical cognitive function due to the occurrence of multiple infarcts in the cerebral vascularization throughout the gray and white matter. Current therapies of MID mostly focus only on slowing down MID progression and symptomatic medications. A novel therapy which is able to provide both preventive and curative properties for MID is of high interest. The purpose of this review is to identify the potential of Compound 21 (C21) gelatin nanoparticle through the nose-to-brain route as therapy for MID. C21, an angiotensin II type 2 receptor (AT2R) agonist, has shown to reduce the size of cerebral infarct in rodent models, resulting in the preservation and improvement of overall cognitive function and prevention of secondary neurodegenerative effects. It is also shown that C21 decreases neuronal apoptosis, improves damaged axons, and encourage synapse development. The challenge remains in preventing systemic AT2R activation and increasing its low oral bioavailability which can be overcome through nose-to-brain administration of C21. Nose-to-brain drug delivery of C21 significantly increases drug efficiency and limits C21 exposure in order to specifically target the multiple infarcts located in the cerebral cortex. Adhering C21 onto gelatin nanoparticles may enable longer contact time with the olfactory and the trigeminal nerve endings, increasing the potency of C21. In summary, treatment of C21 gelatin nanoparticle through nose-to-brain delivery shows high potential as therapy for vascular dementia. However, clinical trials must be further studied in order to test the safety and efficacy of C21.

Abstract Epilepsy, a neurological illness, is characterized by recurrent uncontrolled seizures. There are many treatments of options that can be used as the therapy of epilepsy. However, anti-seizure medications as the primary treatment choice for epilepsy show many possible adverse effects and even pharmacoresistance to the therapy. High Mobility Group Box 1 (HMGB1) as an initiator and amplifier of the neuroinflammation is responsible for the onset and progression of epilepsy by overexpressing P-glycoprotein on the blood brain barrier. HMGB1 proteins then activate TLR4 in neurons and astrocytes, in which proinflammatory cytokines are produced. Anti-HMGB1 mAb works by blocking the HMGB1, reducing inflammatory activity in the brain that may affect epileptogenesis. Through the process, anti-HMGB1 mAb reduces the TLR4 activity and other receptors that may involve in promote signal of epilepsy such as RAGE. Several studies have shown that anti-HMGB1 has the potential to inhibit the increase in serum HMGB1 in plasma and brain tissue. Further research is needed to identify the mechanism of the inhibiting of overexpression of P-glycoprotein through anti-HMGB1 mAb.

Abstract Alzheimer's disease (AD) is a neurodegenerative disease closely related to the accumulation of beta-amyloid (Aβ) plaques. Growth differentiation factor 11 (GDF11) is one of the proteins that play a role in the aggravation of AD. Decreased concentration of GDF11 disrupts regenerative nervous system, blood vessels, and various vital systems. Low levels of GDF11 with age can be overcome with recombinant GDF11 (rGDF11) to rejuvenate the regenerative effect. Based on research results, rGDF11 enhance the proliferation rate of neuronal precursor cells as well as angiogenesis. rGDF11 can replace lost levels of GDF11, overcome astrogliosis and activation of nerve cell microglia. Therapeutic effect of rGDF11 leads to an improved prognosis in AD patients by neurogenesis and angiogenesis. The prospects of rGDF11 in the treatment of AD have great potential for further research in the future.

Introduction Osteoarthritis (OA) is a joint condition that causes significant impairment of the chondrocyte. The gradual degradation of the cartilage lining of one or more freely moving joints, as well as persistent inflammation, are the causes of osteoarthritis. Current medication focuses on alleviating symptoms rather than curing the condition. Methods This review article was completed by searching for information with the keywords “Fibroblast Growth Factor Receptor-1”, “Extracellular Vesicle”, and “Osteoarthritis” in various journals in several search engines. Out of 102 publications found, 95 were suitable to be studied. Results The upregulated amount of fibroblast growth factor receptors (FGFR1) signaling suggesting the progression of degenerative cartilage that commonly seen in osteoarthritis (OA) patients. Several studies showed that the involvement of extracellular vesicles (EV) derived from MSCs could enhance cartilage repair and protect the cartilage from degradation. EVs have the potential to deliver effects to specific cell types through ligand-receptor interactions and several pathway mechanisms related with the FGFR1. EVs and FGFR1 have been postulated in recent years as possible therapeutic targets in human articular cartilage. Conclusions The protective benefits on both chondrocytes and synoviocytes in OA patients can be achieved by administering the MSC-EVs that may also stimulate chondrocyte proliferation and migration. EVs have a promising potential to become a novel therapy for treating patients with OA. However, further research is needed to discover possible application of this therapy.