Treatment Of Disorders Research Articles

Nanotechnology - An advanced dental innovation

Researchers are interested in exploring the possible uses and advantages of nanotechnology compared to traditional materials, particularly in the domains of dentistry and medicine. The study and creation of materials, tools, systems with distinct biological, chemical, physical characteristics from those found in larger system is known as nanotechnology. Numerous advancements and improvement in oral disease prevention, diagnosis, and treatment are possible because of nanotechnology. Recent Nano - technology breakthrough developments in dentistry are progressively providing a viable therapeutic option for a wide range of dental problems. The purpose of this review was to provide an overview role of nanotechnology in dentistry, as well as to evaluate its application in the prevention and treatment of oral disorders, along with providing crucial new updates on the various nanotechnology – based techniques for dental disease management. The current review will also assist the reader in comprehending Nano science, as well as its benefits and drawbacks, by discussing its ethical, social, and health consequences. In addition, Nano -applications in dental diagnostics and their function in dentistry will be discussed.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear. AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation. METHODS Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes. RESULTS Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets. CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

Rapid biotransformation of STW 5 constituents by human gut microbiome from IBS- and non-IBS donors.

STW 5 is an herbal medicinal product with proven clinical efficacy in the treatment of functional gastrointestinal disorders, like functional dyspepsia and irritable bowel syndrome (IBS). The effects of STW 5 on fecal microbial communities and metabolite production effects have been studied in an experimental model with fecal samples from individuals with and without IBS. While only minor taxonomic disparities were noted between IBS- and non-IBS samples and upon treatment with STW 5, rapid metabolic turnover of STW 5 components into specific degradation products with reported anti-inflammatory, cytoprotective, or spasmolytic activities was observed, which may be relevant for the pharmacological activity of STW 5.

Updates in the treatment of eating disorders in 2023: a year in review in eating disorders: the Journal of treatment & Prevention.

Empirical evidence is unequivocal in illustrating that the majority of patients with eating disorders will not fully recover during treatment. To that end, the need for optimized treatment approaches and improved patient outcomes cannot be overstated. While empirical efforts are underway to optimize outcomes, this article reviews treatment-related research findings published in Eating Disorders: The Journal of Treatment & Prevention during 2023. Importantly, this review encapsulates research addressing (i) between-session patient behaviors, (ii) the integration of technology into treatment approaches, (iii) methods to augment emotional regulation in the context of eating disorder treatment, (iv) methods to measure progress, and potentially risk markers for patient dropout, during treatment, (v) optimizing treatment approaches for inpatient settings, and (vi) augmenting family therapy-based approaches. Incorporating novel technological advances may be critical in enhancing the scalability of eating disorder treatments, since treatment uptake remains an ongoing challenge for the field. Moreover, expanding the scope of non-outpatient eating disorder treatment settings, while ensuring fidelity to theoretical models developed in outpatient settings, is critical as treatment is effectively administer across the spectrum of levels of patient care.

Prevalence of Mental Health Disorders and Their Associated Risk Factors Among People Living with HIV in Rwanda: A Cross-Sectional Study.

While life expectancy of people living with HIV is increasing, their burden of non-communicable diseases, including mental health disorders, is growing as well. The aim of this study is to investigate the prevalence and identify the risk factors associated with mental health disorders among this population in Rwanda. This cross-sectional study enrolled people living with HIV from 12 HIV clinics across Rwanda using random sampling. Trained HIV nurses conducted the Mini International Neuropsychiatric Interview to estimate the prevalence of major depressive episode, post-traumatic stress disorder, and generalized anxiety disorder. Sociodemographic, psychosocial, and HIV-related data were also collected. Associated risk factors for being diagnosed with one of the mental health disorders were assessed using modified Poisson regression with robust error variance. Of 428 participants, 70 (16.4%) had at least one mental health disorder with major depressive episode being most prevalent (n = 60, 14.0%). Almost all participants were adherent to antiretroviral therapy (n = 424, 99.1%) and virally suppressed (n = 412, 96.9%). Of those diagnosed with a mental health disorder, only few were aware of (n = 4, 5.7%) or under treatment for this mental health disorder (n = 5, 7.2%). Mental health disorders were associated with experiences of HIV-related stigma and discrimination (aRR = 2.14, 95%CI 1.30-3.53, p = 0.003). The results demonstrate underdiagnosis and undertreatment of mental health disorders among Rwandan People Living with HIV. Using HIV nurses to diagnose mental health disorders could serve as a low-cost strategy for integrating mental health care with existing HIV services and could inspire the implementation in other low-resource settings.

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Assisted Versus Unassisted Domiciliary Alcohol Detoxification: A Randomized Controlled Trial

Background: Detoxification stands as a crucial phase in the treatment of alcohol use disorders (AUD), yet only limited data is available on the outcomes of home-based detoxification. Assisted domiciliary detoxification involves monitoring an individual’s withdrawal progress, while offering psychosocial support and detoxification services in the comfort of their home. Aim: To study outcomes of assisted over routine domiciliary alcohol detoxification in randomized controlled trials. Methodology: 100 consenting male patients who were advised of domiciliary detoxification were randomized into intervention ( n = 49) and control ( n = 51) groups. A predesigned semi-structured questionnaire was used to assess the socio-demographic and drinking-related variables. Both groups received routine care for alcohol withdrawal from respective treating doctors. Additionally, the intervention group received two sessions of brief intervention for alcohol and daily phone call assistance. Records were kept for adverse events. Phone calls were discontinued once detoxification was completed. Outcomes were measured for successful completion of detoxification and abstention from alcohol at the end of one month. Results: The intervention group had significantly higher successful detoxification rates (85.7% vs. 62.7%, p = .008) and significantly higher abstinence days at the end of one month compared to the control group (22 vs. 10 days, p < .001) with an effect size of 1.2 (confidence interval (CI) 0.69–1.53). Conclusion: This study demonstrates that receiving assistance in the acute phase of domiciliary detoxification helps in a successful detoxification and achieving a significant level of abstinence at the end of one month compared to the control group.

Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Nutritional and therapeutic potentials of Carica papaya Linn. seed: A comprehensive review

The health benefits and nutritional value of pawpaw or papaya (Carica papaya Linn.) are well established. The entire papaya plant—including the leaves, fruit, bark, root, juice, seeds and latex - is used for dietary, medicinal and other purposes. However, papaya seeds are the under-exploited part since they are typically seen as waste after the edible fruits have been processed and consumed. Hence, the aim of this review is to document the nutraceutical and therapeutic potential of Carica papaya seeds with a view of enhancing its prospect in drug development. The following title search criteria were used “Carica papaya” OR “Papaya” OR “Pawpaw OR C. papaya” AND “seed” OR “seed oil”; while “fruits OR leaves OR stem OR root OR juice OR latex” were excluded. The articles used for this research were limited to the original research articles and those written in English Language only. The seeds which are often seen as waste products offer countless possibilities for developing new nutritional supplements and medicines due to the huge vital micronutrients and a variety of secondary metabolites that have been reported to be embedded in them. Papaya seeds contain beneficial phytochemicals such as carotenoids, flavonoids, alkaloids, phytosterols and tocopherols. These substances, have intriguing nutraceutical qualities and are important in the treatment and amelioration of several medical disorders. Benzyl glucosinolates, caricin, fatty acids, crude fibre, carpaine, glucotropaeolin, benzyl isothiocyanate, crude protein, benzyl thiourea, hentriacontane, ß-sitostrol and enzymes (myrosinase and papain) were discovered as nutritional components in papaya seeds. Papaya seeds may be used medicinally as antioxidant, antidiabetic, antiulcerogenic, liver cirrhosis treatment and menstrual cycle modulation.

CYTOTOXIC ACTIVITY OF FRACTIONS AND COMPOUNDS FROM PEPEROMIA PELLUCIDA

Peperomia pellucida is a widely distributed herb and commonly used in folk medicine for the treatment of various disorders. The present study reported the isolation, elucidation of compounds from the whole plant and their cytotoxic activities on Hep G2 (HB - 8065TM, hepatocellular carcinoma), A549 (CCL-185™, pulmonary adenocarcinoma), and MCF-7 (HTB - 22TM, breast cancer) cell lines. As a result, velutin exhibited the most significant cytotoxicity against Hep G2, A549, and MCF-7 cell lines with IC50 values of 34.00, 30.85, and 41.33 μg/mL, respectively.

The potential value of brief waitlist interventions in enhancing treatment retention and outcomes: a randomised controlled trial

ABSTRACT People with eating disorders are often placed on lengthy waitlists for treatment. This is problematic, as increased time spent on waitlists has been shown to predict dropout. We examined whether providing brief interventions to people on a waitlist improved retention or outcomes in treatment. Participants (N = 85) were referred to a university training clinic for 10-session cognitive behavioural therapy for non-underweight patients with eating disorders (CBT-T). While waitlisted for CBT-T, participants were randomised to one of two waitlist interventions or a control condition. In one waitlist intervention (CRT-Brief), participants received a cognitive remediation therapy session at the start of the waitlist period. In the other waitlist intervention (brief contact), participants were sent a short supportive email and psychoeducation halfway through the waitlist period. The control condition was waitlist as usual. There was no evidence to suggest that the waitlist interventions improved symptoms during the waitlist period or CBT-T. However, participants who received a waitlist intervention were three times more likely to complete treatment. The present study suggests that providing even brief contact while people are waitlisted for eating disorder treatment significantly improves retention. However, replication in a more adequately powered study is required.

The importance of examining early maladaptive schemas in the diagnosis and treatment of obsessive-compulsive disorder

IntroductionThe aim of the study was twofolded: to identify the early maladaptive schemas characteristic of obsessive-compulsive disorder in a Hungarian sample and, to examine the presence and severity of comorbid anxiety and depressive symptoms in the light of early maladaptive schemas.Methods112 participants (58 men and 54 women) diagnosed with OCD were involved in the study. The questionnaire package consisted of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Penn State Worry Questionnaire (PSWQ) and the Schema Questionnaire (SQ).ResultsWe identified five early maladaptive schemas with a direct effect on the manifestation of obsessive-compulsive symptoms: Mistrust-Abuse, Inferiority/Shame, Dependence/Incompetence, Insufficient Self-Control/Self-Discipline and Entitlement/Grandiosity (reversed effect). Based on the severity of the early maladaptive schemas, three significantly different groups could be identified in our sample: patients with mild, moderate and high schema-values. Among the groups significant differences can be found in the appearance and severity of compulsive symptoms, as well as in the presence of anxiety and depressive symptoms. But contrary to our expectations, not the severity, but the numberof the early maladaptive schemas showed a stronger correlation with the symptom variables. An additional result of our study derives from canonical correlation, addressing the relationship among early maladaptive schemas, OCD symptoms, anxiety and depressive symptoms from a new perspective. The results highlight that OCD is only one and not the most serious consequence of personality damage, indicated by early maladaptive schemas.DiscussionThe results of our study suggest that obsessive-compulsive disorder can be divided into several subgroups, which can be separated in terms of symptom severity, comorbid psychiatric symptoms and personality impairment patterns. The relationship between OCD symptom severity and personality impairment seems to be not directly proportional. Our results strengthen the new dimensional view of OCD, which can determine the selection of the appropriate therapeutic treatment method beyond the diagnostic process.

Intra-Articular Platelet-Rich Plasma Injection After Anterior Cruciate Ligament Reconstruction

Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, -2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Chinese Clinical Trial Registry Identifier: ChiCTR2000040262.

Red Algae Compounds: Potential Neuroprotective Agents for Neurodegenerative Disorders

This review explores the potential of compounds derived from red algae (Rhodophyta) as promising neuroprotective agents for treating neurodegenerative disorders. Red algae, abundant in marine environments, contain bioactive compounds with diverse chemical structures and functionalities. Sulfated polysaccharides, primarily agar and carrageenans, stand out as the predominant and widely utilized compounds derived from red algae. Additionally, red algae harbor a spectrum of potential molecules such as essential fatty acids, phycobiliproteins, vitamins, minerals, and secondary metabolites. Extensive research has highlighted the diverse biological activities exhibited by these compounds, including anti-oxidative and anti-inflammatory properties. These compounds show various biological activities that have garnered interest in their therapeutic potential for neurodegenerative diseases. This comprehensive review aims to summarize the current knowledge regarding the extraction, characterization, mechanisms of action, and therapeutic applications of Rhodophyta-derived compounds in the context of neuroprotection and treatment of neurodegenerative disorders.

Absolute and relative outcomes of psychotherapies for eight mental disorders: a systematic review and meta-analysis.

Psychotherapies are first-line treatments for most mental disorders, but their absolute outcomes (i.e., response and remission rates) are not well studied, despite the relevance of such information for health care users, providers and policy makers. We aimed to examine absolute and relative outcomes of psychotherapies across eight mental disorders: major depressive disorder (MDD), social anxiety disorder, panic disorder, generalized anxiety disorder (GAD), specific phobia, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and borderline personality disorder (BPD). We used a series of living systematic reviews included in the Metapsy initiative (www.metapsy.org), with a common strategy for literature search, inclusion of studies and extraction of data, and a common format for the analyses. Literature search was conducted in major bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane Register of Controlled Trials) up to January 1, 2023. We included randomized controlled trials comparing psychotherapies for any of the eight mental disorders, established by a diagnostic interview, with a control group (waitlist, care-as-usual, or pill placebo). We conducted random-effects model pairwise meta-analyses. The main outcome was the absolute rate of response (at least 50% symptom reduction between baseline and post-test) in the treatment and control conditions. Secondary outcomes included the relative risk (RR) of response, and the number needed to treat (NNT). Random-effects meta-analyses of the included 441 trials (33,881 patients) indicated modest response rates for psychotherapies: 0.42 (95% CI: 0.39-0.45) for MDD; 0.38 (95% CI: 0.33-0.43) for PTSD; 0.38 (95% CI: 0.30-0.47) for OCD; 0.38 (95% CI: 0.33-0.43) for panic disorder; 0.36 (95% CI: 0.30-0.42) for GAD; 0.32 (95% CI: 0.29-0.37) for social anxiety disorder; 0.32 (95% CI: 0.23-0.42) for specific phobia; and 0.24 (95% CI: 0.15-0.36) for BPD. Most sensitivity analyses broadly supported these findings. The RRs were significant for all disorders, except BPD. Our conclusion is that most psychotherapies for the eight mental disorders are effective compared with control conditions, but absolute response rates are modest. More effective treatments and interventions for those not responding to a first-line treatment are needed.

Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction).Limitations: The linear model was constructed separately for each region of interest. This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS.

Comprehensive spectroscopic and computational insight into the binding of vanillin with human transferrin: targeting neuroinflammation in Alzheimer’s disease therapeutics

In present times, vanillin stands out as a promising therapeutic molecule that can be implicated in the treatment of neurodegenerative disorders (NDs), notably Alzheimer’s disease (AD). This can be attributed to the highly potent scavenging activity of vanillin against reactive oxygen species (ROS). Oxidative stress leads to generation of ROS that serves a critical role in AD’s pathological progression. It is apparent from various studies that diets rich in polyphenols prevent oxidative stress associated with AD development, implying the crucial role of vanillin in AD therapeutics. It is crucial to maintain iron balance to manage AD associated oxidative stress, unveiling the significance of human transferrin (hTf) that maintains iron homeostasis. Here, we have performed an integrated study of spectroscopic and computational approaches to get insight into the binding mechanism of vanillin with hTf. In the preliminary study, molecular docking deciphered that vanillin primarily occupies the hTf binding pocket, forming multiple interactions with its key residues. Moreover, the binding mechanism was evaluated at an atomistic level employing comprehensive molecular dynamic (MD) simulation. MD analysis demonstrated that binding of vanillin to hTf stabilizes its structure, without inducing any significant alterations in its native conformation. The docked complex was maintained throughout the simulations without changing its original conformation. Essential dynamics analysis further confirms that hTf achieved a stable conformation with vanillin. The outcomes were further supplemented by fluorescence spectroscopy which confirms the formation of stable hTf-vanillin complex. Taken together, the current study unveils the interaction mechanism of vanillin with hTf and providing a platform to use vanillin in AD therapeutics in the context of iron homeostasis.

Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity

Most drugs that target the complement system are designed to inhibit the complement pathway at either the proximal or terminal levels. The use of a natural complement regulator such as factor H (FH) could provide a superior treatment option by restoring the balance of an overactive complement system while preserving its normal physiological functions. Until now, the systemic treatment of complement-associated disorders with FH has been deemed unfeasible, primarily due to high production costs, risks related to FH purified from donors’ blood, and the challenging expression of recombinant FH in different host systems. We recently demonstrated that a moss-based expression system can produce high yields of properly folded, fully functional, recombinant FH. However, the half-life of the initial variant (CPV-101) was relatively short. Here we show that the same polypeptide with modified glycosylation (CPV-104) achieves a pharmacokinetic profile comparable to that of native FH derived from human serum. The treatment of FH-deficient mice with CPV-104 significantly improved important efficacy parameters such as the normalization of serum C3 levels and the rapid degradation of C3 deposits in the kidney compared to treatment with CPV-101. Furthermore, CPV-104 showed comparable functionality to serum-derived FH in vitro, as well as similar performance in ex vivo assays involving samples from patients with atypical hemolytic uremic syndrome, C3 glomerulopathy and paroxysomal nocturnal hematuria. CPV-104 – the human FH analog expressed in moss – will therefore allow the treatment of complement-associated human diseases by rebalancing instead of inhibiting the complement cascade.

Psychopharmacological treatment in patients planned for hip or knee replacement.

Psychopharmacological treatment may be an independent risk factor for increased length of stay and readmission after hip and knee replacement. Thus, temporary perioperative discontinuation may be beneficial. However, little is known regarding the treatments, and not all are feasible to discontinue. Therefore, the aim of this study was to describe the treatments in terms of type, dose, duration, indication and initiating physician to assess the feasibility of temporary perioperative discontinuation. We included 482 patients planned for hip or knee replacement in psychopharmacological treatment for psychiatric disorders from 2021 to 2023 at five orthopaedic departments in Denmark. Most patients were treated with antidepressants (89%); most frequently, either selective serotonin reuptake inhibitors (SSRIs; 48%) or serotonin-norepinephrine reuptake inhibitors (SNRIs; 21%). The majority received monotherapy (70%); most frequently, an SSRI (36%) or an SNRI (12%). Most antidepressants were initiated by general practitioners (71%), and the treatments had lasted for more than a year (87%). The doses of SSRIs/SNRIs were moderate, and the most frequent indication for antidepressants was depression (77%). These results imply that temporary perioperative SSRI/SNRI discontinuation may be feasible in hip and knee replacement patients and support a future randomized controlled trial investigating the potential benefits of temporary discontinuation.