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Journal of Biochemical and Molecular... Jul 2024Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and...
Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aβ1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kβ), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aβ1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.
Topics: Animals; Polyunsaturated Alkamides; Benzodioxoles; Curcumin; Piperidines; Alkaloids; Rats; Cyclophosphamide; Male; Brain Injuries; Rats, Wistar; Brain; Oxidative Stress; Neuroprotective Agents
PubMed: 38953502
DOI: 10.1002/jbt.23760 -
The Chinese Journal of Dental Research Jun 2024To evaluate the effect of entrapment of curcumin within liposomal formulation and the sustained release attitude of the formulated liposomal gel on periodontal defects... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the effect of entrapment of curcumin within liposomal formulation and the sustained release attitude of the formulated liposomal gel on periodontal defects in diabetic patients in clinical and biochemical terms.
METHODS
Thirty diabetic patients with periodontitis were randomly assigned to three equal groups and ten healthy participants were assigned as the control group. Group I was subjected to scaling and root planing (SRP) with application of sustained release liposomal curcumin gel. Group II was subjected to scaling and root planning with application of curcumin gel. Group III was subjected to scaling and root planning with application of placebo gel. Group IV (control group), no intervention was done. The following parameters were evaluated before treatment and after 6 and 12 weeks: plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and total antioxidant capacity (TAC).
RESULTS
All study groups showed improvement in clinical and biochemical parameters that are statistically significant. Upon comparing the results of treatment modalities, the highest improvement was achieved in group I followed by group II then group III.
CONCLUSION
Sustained release liposomal curcumin gel enhanced the antioxidant capacity, decreased the inflammatory mediators and showed more improvement in clinical outcome for treatment of periodontitis in diabetic patients.
Topics: Humans; Curcumin; Liposomes; Delayed-Action Preparations; Male; Female; Middle Aged; Adult; Dental Scaling; Periodontitis; Root Planing; Treatment Outcome; Tumor Necrosis Factor-alpha; Antioxidants; Periodontal Index
PubMed: 38953482
DOI: 10.3290/j.cjdr.b5459607 -
Magnesium Research Jun 2024To evaluate the analgesic effects of intravenous magnesium in patients undergoing thoracic surgery. Randomised clinical trials (RCTs) were systematically identified from... (Meta-Analysis)
Meta-Analysis
To evaluate the analgesic effects of intravenous magnesium in patients undergoing thoracic surgery. Randomised clinical trials (RCTs) were systematically identified from MEDLINE, EMBASE, Google Scholar and the Cochrane Library from inception to May 1st, 2023. The primary outcome was the effect of intravenous magnesium on the severity of postoperative pain at 24 hours following surgery, while the secondary outcomes included association between intravenous magnesium and pain severity at other time points, morphine consumption, and haemodynamic changes. Meta-analysis of seven RCTs published between 2007 and 2019, involving 549 adults, showed no correlation between magnesium and pain scores at 1-4 (standardized mean difference [SMD]=-0.06; p=0.58), 8-12 (SMD=-0.09; p=0.58), 24 (SMD=-0.16; p=0.42), and 48 (SMD=-0.27; p=0.09) hours post-surgery. Perioperative magnesium resulted in lower equivalent morphine consumption at 24 hours post-surgery (mean difference [MD]=-25.22 mg; p=0.04) and no effect at 48 hours (MD=-4.46 mg; p=0.19). Magnesium decreased heart rate (MD = -5.31 beats/min; p=0.0002) after tracheal intubation or after surgery, but had no effect on postoperative blood pressure (MD=-6.25 mmHg; p=0.11). There was a significantly higher concentration of magnesium in the magnesium group compared with that in the placebo group (MD = 0.91 mg/dL; p<0.00001). This meta-analysis provides evidence supporting perioperative magnesium as an analgesic adjuvant at 24 hours following thoracic surgery, but no opioid-sparing effect at 48 hours post-surgery. The severity of postoperative pain did not significantly differ between any of the postoperative time points, irrespective of magnesium. Further research on perioperative magnesium in various surgical settings is needed.
Topics: Humans; Pain, Postoperative; Magnesium; Randomized Controlled Trials as Topic; Thoracic Surgical Procedures; Analgesia
PubMed: 38953415
DOI: 10.1684/mrh.2024.0522 -
Journal of Pain Research 2024Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA)...
PURPOSE
Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA) and gout, persistent inflammation due to long-term overexpression of several key cytokines has been linked to neuronal hypersensitivity and damage within the joints. Ultimately, a subset of patients develop chronic pain. Pharmacologic treatment of joint pain involves the use of analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, as well as intra-articular injections of corticosteroids and hyaluronic acid. However, NSAIDs are short-acting and fail to alleviate severe pain, opioids are generally ineffective at managing chronic pain, and all therapeutic options involve increased risks of serious side effects.
METHODS
We explored the therapeutic and analgesic effects of transforming growth factor-β-activated kinase 1 (TAK1) inhibition in both the monoiodoacetate (MIA) and monosodium urate (MSU) models of joint pain as an innovative strategy for alleviating chronic inflammatory pain. Mechanical allodynia (Von Frey), weight-bearing and histological changes were measured in separate groups of rats receiving either the selective TAK1 inhibitor, HS-276, gabapentin or vehicle.
RESULTS
Our data support that TAK1 inhibition effectively prevented the development of mechanical allodynia and differential weight-bearing in the MIA model. In the MSU model of gouty arthritis, treatment with HS-276 significantly reduced mechanical allodynia and knee edema in female rats, but not male rats. Histological evaluation of effected joints in both models showed that HS-276 treatment significantly reduced disease-induced degradation of the joint.
CONCLUSION
Our results support that TAK1 is a critical signaling node in inflammatory joint diseases such as OA and gouty arthritis. Selective pharmacological inhibition significantly attenuated several aspects of the disease, including joint degeneration and mechanical pain. Thus, TAK1 is a novel therapeutic target for the treatment of painful inflammatory joint diseases.
PERSPECTIVE
This article reports on the therapeutic potential of TAK1 in the treatment of chronic inflammatory joint diseases such as OA and gout. Using the selective TAK1 inhibitor, HS-276, we show the therapeutic and analgesic effects of TAK1 inhibition in two preclinical murine models of inflammatory joint pain.
PubMed: 38952995
DOI: 10.2147/JPR.S451409 -
PeerJ 2024Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and...
BACKGROUND
Andrographolide (Andro), an extract of (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear.
METHODS
The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy.
RESULTS
Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both and . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro.
CONCLUSION
Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
Topics: Reactive Oxygen Species; Diterpenes; Pancreatic Neoplasms; Autophagy; Protein Deglycase DJ-1; Animals; Humans; Mice; Cell Line, Tumor; Apoptosis; Xenograft Model Antitumor Assays; Mice, Nude
PubMed: 38952980
DOI: 10.7717/peerj.17619 -
Cureus Jun 2024Awake craniotomy (AC) is sometimes aborted due to poor arousal and restlessness. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has sedative, analgesic, and...
Awake craniotomy (AC) is sometimes aborted due to poor arousal and restlessness. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has sedative, analgesic, and anesthetic-sparing effects, with a low risk of respiratory depression, making it effective for intraoperative pain and agitation during the awake phase. We report a case in which AC was successfully performed in combination with low-dose continuous administration of DEX during reoperation in a patient who experienced poor arousal and restlessness during their first surgery, leading to the abandonment of AC. The patient is a 48-year-old male who is scheduled for AC reoperation. Two years ago, the first AC was scheduled and performed under anesthesia with propofol and remifentanil. However, AC was abandoned due to poor intraoperative arousal and restlessness. At reoperation, general anesthesia was induced with propofol and continuous administration of remifentanil (0.1 µg/kg/min); following anesthesia induction (continuous infusion of propofol, remifentanil, and a bolus infusion of fentanyl), DEX was also administered (0.2 µg/kg/hour). We performed a scalp nerve block. Before the awake phase, the propofol dose was decreased as was DEX to 0.1 µg/kg/hour, and propofol and remifentanil were discontinued. The patient gradually awoke without any agitation and restlessness 24 min after stopping propofol and remifentanil and could perform language tasks without any complications. In this case, AC was successfully performed in combination with continuous low-dose administration of DEX at the time of reoperation in a patient who experienced poor arousal and restlessness during their first operation and had to discontinue AC.
PubMed: 38952610
DOI: 10.7759/cureus.61506 -
Cureus Jun 2024Osteopoikilosis (OP) is a rare genetic bone dysplasia that causes dense patches in the trabecular bone and occurs in one in 50,000 people. The exact cause is unknown,...
Osteopoikilosis (OP) is a rare genetic bone dysplasia that causes dense patches in the trabecular bone and occurs in one in 50,000 people. The exact cause is unknown, but it could be due to mutations in the LEM domain-containing gene 3. Two cases were discovered incidentally in a clinic. The first case involved the mother, a 35-year-old woman with type 2 diabetes and dyslipidemia who presented with left ankle and right forearm pain after falling downstairs. Physical examination revealed mild swelling and tenderness at the left ankle, and X-ray examination revealed multiple small sclerotic lesions. The patient was diagnosed with OP. Analgesics, ankle support, and follow-up care were provided. The second case involved the son, a 14-year-old boy who had occasional pain in his right foot. A physical examination was normal. An X-ray of the right foot showed multiple homogeneous sclerotic lesions. He was diagnosed with familial OP and given analgesics for his pain.
PubMed: 38952582
DOI: 10.7759/cureus.61477 -
Veterinary Medicine and Science Jul 2024Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of...
BACKGROUND
Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.
OBJECTIVES
The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.
METHODS
The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis.
RESULTS
The elimination half-life (t) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.
CONCLUSIONS
While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Topics: Animals; Oncorhynchus mykiss; ortho-Aminobenzoates; Biological Availability; Anti-Inflammatory Agents, Non-Steroidal; Administration, Oral; Blood Proteins; Injections, Intramuscular; Protein Binding; Injections, Intravenous; Half-Life
PubMed: 38952278
DOI: 10.1002/vms3.1533 -
Journal of Biochemical and Molecular... Jul 2024Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human...
Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 μM, and the IC50 of Tilianin for H1299 cells was 44.6 μM. Functionally, 0.5 nM sufentanil and 10 μM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 μM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 μM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 μM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Sufentanil; Lung Neoplasms; Animals; Mice; Apoptosis; Xenograft Model Antitumor Assays; A549 Cells; Mice, Nude; Drug Synergism; Cell Line, Tumor; Mice, Inbred BALB C; Antineoplastic Agents; Chondroitin Sulfates; Amphibian Venoms
PubMed: 38952040
DOI: 10.1002/jbt.23761 -
BMC Complementary Medicine and Therapies Jun 2024Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC).
METHODS
We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance).
DISCUSSION
Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans.
TRIAL REGISTRATION
This protocol is registered at clinicaltrials.gov under study number NCT06213233.
Topics: Humans; Cannabidiol; Chronic Pain; Veterans; Double-Blind Method; United States; Analgesics; Male; Pragmatic Clinical Trials as Topic; Female; Adult; Middle Aged
PubMed: 38951902
DOI: 10.1186/s12906-024-04558-3