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Pharmaceuticals (Basel, Switzerland) May 2024Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing... (Review)
Review
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.
PubMed: 38794180
DOI: 10.3390/ph17050610 -
Vaccines May 2024COVID-19 vaccines represent effective public health measures in contrasting the pandemic worldwide. However, protection at the individual-level, which is of crucial... (Review)
Review
COVID-19 vaccines represent effective public health measures in contrasting the pandemic worldwide. However, protection at the individual-level, which is of crucial importance from an occupational health perspective, is commonly assessed by a serological correlate of protection (CoP) for SARS-CoV-2, which has not yet been determined. The emergence of variants of concern (VOCs) that have shown high rates of breakthrough infections has further complicated the understanding of immune protection against infection. To define a potential serological correlate of protection induced by the COVID-19 vaccination, a systematic review and meta-analysis was performed to summarize the evidence concerning the binding antibody concentration corresponding to a protective effect. Eighteen and four studies were included in the qualitative and quantitative analyses, respectively. The protection against infection was shown for anti-receptor-binding domain (RBD) titers ranging from 154 to 168.2 binding antibody units (BAU)/mL during the pre-Omicron period, while ranging from 1235 to 3035 BAU/mL in the Omicron period. Pooling the results from the studies concerning anti-RBD and anti-Spike antibody titer, we found a mean of 1341.5 BAU/mL and 1400.1 BAU/mL, respectively. These findings suggest that although a fixed serological threshold corresponding to protection against different SARS-CoV-2 variants is not yet definable, higher binding antibody concentrations are associated with increased protective effects.
PubMed: 38793745
DOI: 10.3390/vaccines12050494 -
Viruses Apr 2024This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted... (Review)
Review
This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Hepatitis B virus; Adaptive Immunity; T-Lymphocytes, Regulatory; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Hepatitis B; Hepatitis B, Chronic; CD4-Positive T-Lymphocytes; T-Lymphocytes; Immunotherapy
PubMed: 38793588
DOI: 10.3390/v16050707 -
Journal of Personalized Medicine Apr 2024Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human... (Review)
Review
Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25-30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively.
PubMed: 38793045
DOI: 10.3390/jpm14050463 -
Journal of Clinical Medicine May 2024We conducted a comprehensive investigation to explore the pathological expression of the CXCR4 receptor in lymphoproliferative disorders (LPDs) using [Ga]Ga-Pentixafor... (Review)
Review
We conducted a comprehensive investigation to explore the pathological expression of the CXCR4 receptor in lymphoproliferative disorders (LPDs) using [Ga]Ga-Pentixafor PET/CT or PET/MRI technology. The PICO question was as follows: What is the diagnostic role (outcome) of [Ga]Ga-Pentixafor PET (intervention) in patients with LPDs (problem/population)? The study was written based on the reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, and it was registered on the prospective register of systematic reviews (PROSPERO) website (CRD42024506866). A comprehensive computer literature search of Scopus, MEDLINE, Scholar, and Embase databases was conducted, including articles indexed up to February 2024. To the methodological evaluation of the studies used the quality assessment of diagnosis accuracy studies-2 (QUADAS-2) tool. Of the 8380 records discovered, 23 were suitable for systematic review. Fifteen studies (on 571 LPD patients) focused on diagnosis and staging, and eight trials (194 LPD patients) assessed treatment response. The main conclusions that can be inferred from the published studies are as follows: (a) [Ga]Ga-Pentixafor PET may have excellent diagnostic performance in the study of several LPDs; (b) [Ga]Ga-Pentixafor PET may be superior to [F]FDG or complementary in some LPDs variants and settings; (c) multiple myeloma seems to have a high uptake of [Ga]Ga-Pentixafor. Overall, this technique is probably suitable for imaging, staging, and follow-up on patients with LPD. Due to limited data, further studies are warranted to confirm the promising role of [Ga]Ga-Pantixafor in this context.
PubMed: 38792485
DOI: 10.3390/jcm13102945 -
Journal of Clinical Medicine May 2024: This study aimed to evaluate the efficacy of anti-interleukin-1 therapeutics for treating knee osteoarthritis (KOA). Our research included interleukin-1 (IL-1)... (Review)
Review
Efficacy of Anti-Interleukin-1 Therapeutics in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials from the Years 2000 to 2023.
: This study aimed to evaluate the efficacy of anti-interleukin-1 therapeutics for treating knee osteoarthritis (KOA). Our research included interleukin-1 (IL-1) inhibitors, IL-1 antibodies and IL-1 receptor antagonists (IL-1 Ras). : We systematically searched PubMed and Mendeley to find randomized control trials (RCTs) or clinical trials (CTs) of anti-interleukin-1 therapeutics in KOA from 2000 to 2023. The outcomes were changes in pain, function and stiffness scores. The research was conducted between November 2023 and January 2024. The risk of bias was assessed using Cochrane Risk of Bias tool RoB 2. : Analysis of the nine included studies showed a statistically significant difference in terms of the pain relief group (SMD = -0.20, 95% CI: -0.39 to -0.01, = 0.0348), physical function improvement (SMD = -0.20, 95% CI: -0.39 to 0.00, = 0.0479) and stiffness reduction (SMD = -0.22, 95% CI: -0.43 to 0.00, = 0.0475) between anti-IL-1 therapeutics and placebo or nonsteroidal anti-inflammatory drugs (NSAIDs). However, when we separately analysed placebo and NSAIDs subgroups, the statistical significance was observed only in the placebo group. Our article was limited by the quality of the included RCTs. Two of the included trials were of poor methodological quality, and five showed selective reporting. : The results of our study suggest that anti-IL-1 therapeutics might have better efficacy in KOA treatment than placebo or NSAIDs; yet, taking into account the limited availability of studies and data concerning anti-IL-1 in osteoarthritis treatment, we think that more high-quality RCTs on this subject are needed.
PubMed: 38792403
DOI: 10.3390/jcm13102859 -
International Journal of Molecular... May 2024Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as... (Meta-Analysis)
Meta-Analysis Review
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
Topics: Humans; Colorectal Neoplasms; Prognosis; Biomarkers, Tumor; Chemokines; Receptors, CXCR4; Disease-Free Survival
PubMed: 38791414
DOI: 10.3390/ijms25105374 -
International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198 -
Medicine May 2024Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses a noteworthy challenge linked to the use of this medication, substantially affecting its clinical applicability and the overall well-being of patients. Therefore, this systematic review aims to comprehensively discuss the GIAEs, providing a basis for clinical therapeutic decisions.
METHODS
We systematically searched 4 independent databases for randomized controlled trials investigating the application of semaglutide in managing type 2 diabetes mellitus. The search period spanned from the inception of the databases to December 2023. We conducted a comprehensive meta-analysis, employing Review Manager 5.4.1 software, to systematically analyze and evaluate potential biases. Our primary emphasis was on assessing the gastrointestinal safety profile of semaglutide.
RESULTS
The outcomes unveiled a noteworthy rise in the collective occurrence of GIAEs across all dosage groups of semaglutide in comparison with the control group (P < .05). Upon further analysis, it was observed that semaglutide showed a heightened occurrence of GIAEs in contrast to the placebo. However, statistically significant distinction was not observed when compared to the reduction of conventional doses or the transition to other types of glucagon-like peptide-1 receptor agonist. Additionally, an extended treatment duration with semaglutide (>30 weeks) demonstrated an association with a certain degree of decrease in the incidence of gastrointestinal events. Funnel plot assessment for publication bias demonstrated high-quality inclusion of studies with no apparent publication bias.
CONCLUSION
The frequency of GIAEs in using semaglutide was observed to be elevated in comparison to the control group. However, it was comparable to other glucagon-like peptide-1 receptor agonist or low-dose treatment regimens. Additionally, an extended treatment duration played a role in decreasing the frequency of GIAEs. These findings provide valuable insights for clinical practice. Nonetheless, further research is crucial to explore supplementary data indicators, informing clinical practices and better serving the interests of patients.
Topics: Humans; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Hypoglycemic Agents; Gastrointestinal Diseases; Randomized Controlled Trials as Topic
PubMed: 38787986
DOI: 10.1097/MD.0000000000038236 -
Renal Failure Dec 2024This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous...
BACKGROUND
This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN).
METHODS
First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3-5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy.
RESULTS
We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9-17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer.
CONCLUSIONS
Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.
Topics: Humans; Glomerulonephritis, Membranous; Prognosis; Thrombospondins; Prevalence; Retrospective Studies; Male; Middle Aged; Female; Adult; Neoplasms; Aged; Kidney
PubMed: 38785304
DOI: 10.1080/0886022X.2024.2355353