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CNS Neuroscience & Therapeutics Jun 2024Islet cell autoantigen 1 (ICA1) is involved in autoimmune diseases and may affect synaptic plasticity as a neurotransmitter. Databases related to Alzheimer's disease...
AIMS
Islet cell autoantigen 1 (ICA1) is involved in autoimmune diseases and may affect synaptic plasticity as a neurotransmitter. Databases related to Alzheimer's disease (AD) have shown decreased ICA1 expression in patients with AD. However, the role of ICA1 in AD remains unclear. Here, we report that ICA1 expression is decreased in the brains of patients with AD and an AD mouse model.
RESULTS
The ICA1 increased the expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), and disintegrin and metalloprotease 17 (ADAM17), but did not affect protein half-life or mRNA levels. Transcriptome sequencing analysis showed that ICA1 regulates the G protein-coupled receptor signaling pathway. The overexpression of ICA1 increased PKCα protein levels and phosphorylation.
CONCLUSION
Our results demonstrated that ICA1 shifts APP processing to non-amyloid pathways by regulating the PICK1-PKCα signaling pathway. Thus, this study suggests that ICA1 is a novel target for the treatment of AD.
Topics: Amyloid beta-Protein Precursor; Animals; Protein Kinase C-alpha; Signal Transduction; Humans; Alzheimer Disease; Mice; Carrier Proteins; Nuclear Proteins; Male; Mice, Transgenic; Female; Mice, Inbred C57BL; Amyloid Precursor Protein Secretases; Brain; Cell Cycle Proteins
PubMed: 38884369
DOI: 10.1111/cns.14754 -
The Journal of Dermatological Treatment Dec 2024Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.
Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.
Topics: Humans; Botulinum Toxins, Type A; Double-Blind Method; Skin Aging; Female; Middle Aged; Male; Adult; Forehead; Treatment Outcome; Injections, Intramuscular; Asian People; Neuromuscular Agents; Patient Satisfaction
PubMed: 38880494
DOI: 10.1080/09546634.2024.2359511 -
Clinical Proteomics Jun 2024Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis,...
BACKGROUND
Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.
METHODS
Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.
RESULTS
High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.
CONCLUSIONS
GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.
PubMed: 38879494
DOI: 10.1186/s12014-024-09492-7 -
Medicine Jun 2024Botulinum toxin (BoNT) injection serves as the primary modality for addressing hemifacial spasm (HFS) and blepharospasm (BFS), which are prevalent movement disorders... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Botulinum toxin (BoNT) injection serves as the primary modality for addressing hemifacial spasm (HFS) and blepharospasm (BFS), which are prevalent movement disorders affecting the craniofacial region. However, even though the short-term effectiveness of the botulinum injection may reach over 80%, the long-term effectiveness is still a debatable point Herein, we aim to investigate whether facial self-exercise following the BoNT injection can extend the time period of effectiveness.
METHODS
In this study, 51 volunteers who received Onabotilinumtoxin A (BoNTA) treatment for the diagnosis of HFS or BFS, were randomized into 2 groups. A detailed instruction about the self-exercise was given by an experienced physician to the subjects in Group 1. Volunteers were asked to repeat the exercise program afterward and continue to each movement for 5 seconds, to repeat each movement 10 times with a 10-second break, every day, 3 times a week for 1 week. hemifacial spasm grating scale (HSGS) and Jankovic scales were used to assess the efficacy of the treatment.
RESULTS
Both groups are similar to each other based on demographic features and the severity of the diseases. According to HSGS and Jankovic scales, at the end of the first month, there was no significant difference between the groups. At the end of the third month, the improvement achieved in the first month remained the same in each parameter in Group 1. On the other hand, in Group 2, most of the values returned to the baseline.
CONCLUSION
Facial self-exercise following the botulinum toxin application may extend the period of effectiveness of botulinum toxin treatment the subjects with HFS and BFS.
Topics: Humans; Female; Male; Middle Aged; Hemifacial Spasm; Botulinum Toxins, Type A; Blepharospasm; Neuromuscular Agents; Treatment Outcome; Exercise Therapy; Aged; Adult
PubMed: 38875371
DOI: 10.1097/MD.0000000000038215 -
Scientific Reports Jun 2024One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective...
One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.
Topics: Animals; Dogs; Nerve Growth Factor; Platelet-Rich Plasma; Vascular Endothelial Growth Factor A; Cystitis; Matrix Metalloproteinase 9; Male; Matrix Metalloproteinase 2; Disease Models, Animal; Uropathogenic Escherichia coli; Escherichia coli Infections; Down-Regulation; Urinary Tract Infections
PubMed: 38871929
DOI: 10.1038/s41598-024-63760-y -
Biomedicine & Pharmacotherapy =... Jul 2024Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and...
Cardioprotective effects of the aqueous extract of Echinops cephalotes on myocardial ischemia-reperfusion in rats by modulation of MMP-2, MMP-9, TIMP, and oxidative stress.
Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and anti-inflammatory characteristics. The major purpose of the present study was to investigate the cardioprotective benefits of Echinops cephalotes (Ech) against myocardial ischemia-reperfusion (MI/R) injury. Male Wistar rats were randomly allocated to three groups: sham, MI, and MI + Ech. The left coronary artery (LAD) was blocked for 30 minutes to induce MI. In the treatment group, rats were given 150 mg/kg/day of Ech extract for 28 days. Aqueous extracts were made from Echinops plants. To study heart function, fibrosis, cardiac damage indicators, and oxidative stress factors, echocardiography, Masson's trichrome staining, and biochemical tests were used. The expression of matrix metalloproteinase 2 and 9 (MMP2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) was determined using Western blotting. Tissue damage was assessed using hematoxylin and eosin staining. MI group exhibited significantly reduced ejection fraction (EF) and fractional shortening (FS), enhanced levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), cardiac Troponin I (cTnI), and malondialdehyde (MDA), as well as a decrease in the Glutathione (GSH) tissue content, reduced activity of superoxide dismutase (SOD), increasing fibrosis, upregulations of MMP-2 and MMP-9, and reduction of TIMP compared to the sham group. The findings suggest that Ech in particular, could be a promising therapeutic agent to reduce the damage in MI by targeting oxidative stress and modulating the activities of matrix metalloproteinases and their tissue inhibitors.
Topics: Animals; Male; Oxidative Stress; Rats, Wistar; Matrix Metalloproteinase 2; Plant Extracts; Matrix Metalloproteinase 9; Myocardial Reperfusion Injury; Cardiotonic Agents; Rats; Myocardium; Tissue Inhibitor of Metalloproteinases; Fibrosis; Water; Antioxidants
PubMed: 38870633
DOI: 10.1016/j.biopha.2024.116927 -
Cephalalgia : An International Journal... Jun 2024There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA...
BACKGROUND
There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit.
METHODS
Retrospective chart review with case series.
RESULTS
Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2-7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up.
CONCLUSION
From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.
Topics: Humans; Female; Craniotomy; Botulinum Toxins, Type A; Male; Middle Aged; Adult; Cicatrix; Retrospective Studies; Follow-Up Studies; Cranial Sutures; Treatment Outcome
PubMed: 38870368
DOI: 10.1177/03331024241259452 -
PloS One 2024Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis....
Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.
Topics: Animals; Ureteral Obstruction; Fibrosis; Fibronectins; Mice; Matrix Metalloproteinase 2; Signal Transduction; Transforming Growth Factor beta1; Cell Adhesion Molecules; Epithelial-Mesenchymal Transition; Male; Humans; Kidney Diseases; Kidney; Mice, Inbred C57BL; Cell Line; Disease Models, Animal; Periostin
PubMed: 38870184
DOI: 10.1371/journal.pone.0299389 -
MicrobiologyOpen Jun 2024The G protein-coupled estrogen receptor, also known as GPER1 or originally GPR30, is found in various tissues, indicating its diverse functions. It is typically present...
The G protein-coupled estrogen receptor, also known as GPER1 or originally GPR30, is found in various tissues, indicating its diverse functions. It is typically present in immune cells, suggesting its role in regulating immune responses to infectious diseases. Our previous studies have shown that G-1, a selective GPER agonist, can limit the pathogenesis mediated by Staphylococcus aureus alpha-hemolysin (Hla). It aids in clearing bacteria in a mouse skin infection model and restricts the surface display of the Hla receptor, ADAM10 (a disintegrin and metalloprotease 10) in HaCaT keratinocytes. In this report, we delve into the modulation of GPER in human immune cells in relation to the NLRP3 inflammasome. We used macrophage-like differentiated THP-1 cells for our study. We found that treating these cells with G-1 reduces ATP release, decreases the activity of the caspase-1 enzyme, and lessens cell death following Hla intoxication. This is likely due to the reduced levels of ADAM10 and NLRP3 proteins, as well as the decreased display of the ADAM10 receptor in the G-1-treated THP-1 cells. Our studies, along with our previous work, suggest the potential therapeutic use of G-1 in reducing Hla susceptibility in humans. This highlights the importance of GPER in immune regulation and its potential as a therapeutic target.
Topics: ADAM10 Protein; NLR Family, Pyrin Domain-Containing 3 Protein; Humans; Receptors, G-Protein-Coupled; Hemolysin Proteins; Inflammasomes; Bacterial Toxins; THP-1 Cells; Receptors, Estrogen; Amyloid Precursor Protein Secretases; Staphylococcus aureus; Membrane Proteins; Caspase 1; Adenosine Triphosphate; Macrophages; Dipeptides; Hydroxamic Acids
PubMed: 38867416
DOI: 10.1002/mbo3.1423 -
Nature Communications Jun 2024Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating...
Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors. Specifically, fusogenic liposomes are loaded with gold-containing Auranofin (AUR) and inserted with multivariate-gated aptamer assemblies (ACP) and PD-L1 aptamers in the lipid membrane, potentiating melanoma-targeted AUR delivery while transferring ACP onto cell surface through selective membrane fusion. AUR amplifies IR-induced immunogenic death of melanoma cells to release antigens and damage-associated molecular patterns such as adenosine triphosphate (ATP) for triggering adaptive antitumor immunity. AUR-sensitized radiotherapy also upregulates matrix metalloproteinase-2 (MMP-2) expression that combined with released ATP to activate ACP through an "and" logic operation-like process (AND-gate), thus triggering the in-situ release of engineered cytosine-phosphate-guanine aptamer-based immunoadjuvants (eCpG) for stimulating dendritic cell-mediated T cell priming. Furthermore, AUR inhibits tumor-intrinsic vascular endothelial growth factor signaling to suppress infiltration of immunosuppressive cells for fostering an anti-tumorigenic TME. This study offers an approach for solid tumor treatment in the clinics.
Topics: Liposomes; Aptamers, Nucleotide; Animals; Mice; Cell Line, Tumor; Immunotherapy; Melanoma; Humans; Tumor Microenvironment; Matrix Metalloproteinase 2; Gold; Mice, Inbred C57BL; Female; B7-H1 Antigen; Adenosine Triphosphate
PubMed: 38866788
DOI: 10.1038/s41467-024-49482-9