Injection Of Normal Saline Research Articles

Senkyunolide I ameliorates thoracic aortic aneurysm and dissection in mice via inhibiting the oxidative stress and apoptosis of endothelial cells

BackgroundThoracic aortic aneurysm and aortic dissection (TAAD) is one of the most fatal cardiovascular diseases. Senkyunolide I (SEI) is a component of traditional Chinese medicine with remarkable anti-inflammatory properties and exhibits remarkable protective effects, but its impact on TAAD remains unclear. Our study aimed to explore the role of SEI in a murine model of TAAD and further explore the immunopharmacological mechanism. Methods and materialsThe in vivo model were assessed using echocardiography, gross anatomy, and tissue staining. Western blot and immunofluorescence were performed to evaluate the effects of SEI in vivo and in vitro. A SEI solution injection containing 1 % dimethyl sulfoxide (DMSO) was administered intraperitoneally to the TAAD model group, while a normal saline injection comprising 1 % DMSO was administered to the sham group. ResultsSEI prevented TAAD formation induced by BAPN/Ang II and reduced the TAAD incidence in mice. SEI treatment significantly inhibited the degradation of collagen and elastin fibers in the extracellular matrix. Furthermore, it reduced the expression of inflammatory factors in the aortic intima. Western blot analysis revealed that SEI-treated mice showed a significant decrease in apoptosis-related protein levels in the aorta compared with the TAAD group. PI3K, Akt, and mTOR in the SEI treatment group were significantly lower than in the model group. SEI could also attenuate H2O2-induced Human umbilical vein endothelial cells (HUVECs) damage and reverse the decline in migrant cells. The apoptosis of HUVECs was considerably reduced by the SEI treatment. ConclusionsConclusively, SEI may alleviate the progression of TAAD by suppressing the PI3K/Akt/NF-κB signaling pathway. The SEI's ability to inhibit inflammation and oxidative stress opens the way to restore the function of endothelial cells and vascular homeostasis, and thus to provide novel and promising options for the treatment of TAAD patients.

Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway

To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1β (P < 0.01), enhanced renal expressions of TNF-α, IL-1β and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1β (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.

Comparison of the effects of botulinum toxin type A hamstring muscle injection combined with periarticular injection and simple periarticular injection on early pain and functional recovery after total knee arthroplasty

Objective: This study was designed to compare the effects of hamstring muscle injection of botulinum toxin type A (BoNT/A) combined with periarticular injection to those of simple periarticular injection alone, in terms of early pain reduction and functional recovery following total knee arthroplasty (TKA).&#x0D; Methods: This study included 40 patients who underwent elective unilateral TKA at our hospital from February 2021 to December 2021. The patients were randomly assigned to either the experimental group (BoNT/A injection into the hamstring muscle + periarticular injection, n = 20 cases) or the control group (0.9% normal saline injection into the hamstring muscle + periarticular injection, n = 20 cases). The preoperative and postoperative 3-day HSS scores were compared between the two groups. Postoperative visual analog scale (VAS) pain scores were observed and compared between the two groups. The Lovett grading method was used to evaluate the postoperative muscle strength of both groups. Additionally, postoperative knee joint pain scores, maximum active flexion angle, and any postoperative adverse reactions were observed and compared between the two groups.&#x0D; Results: The experimental group showed significantly lower VAS pain scores than the control group at 24 h, 48 h, and 72 h after the operation, with a statistically significant difference (P &lt; 0.05). Furthermore, compared to the control group, the patients in the experimental group exhibited larger knee joint active flexion angles at 1 day, 3 days, and 5 days post-operation, also demonstrating a statistically significant difference (P &lt; 0.05). These findings hold scientific significance (P &lt; 0.05). Additionally, the combined administration of BoNT/A hamstring muscle injection with periarticular injection exhibited a low incidence of adverse reactions during the perioperative period and had no significant effect on quadriceps muscle strength.&#x0D; Conclusion: The combination of BoNT/A hamstring muscle injection with periarticular injection effectively alleviates early postoperative pain following TKA and promotes early functional recovery of the knee joint.

Analyzing the Potential Antioxidative Effects of Omega-369 in Preventing Acetaminophen-Induced Liver Damage

Background: As acetaminophen (APAP) toxicity has become more common in many countries, related cases of poisoning, whether deliberate or unintentional, have been identified as a key contributor to acute liver failure. Aime: To discover if omega-369 fatty acids could protect the liver of male mice from the effects of acetamiophen. Methods: Thirty-five albino male mice were allocated to one of five groups at random. Group 1 served as the "negative control" and received a single intraperitoneal injection (10 ml/kg) of normal saline on the eleventh day of the test following ten days of receiving liquid paraffin orally at a dose of 10 ml/kg. The liquid paraffin was given to group 2 "positive control". Group 3 received Omega 369 (50 mg/kg/80 ml). Group 4 received Omega 369 (100 mg/kg/35 ml). Group 5 received N-acetylcysteine (100 mg/kg/10 ml). The mice were given Omega-369, N-acetylcysteine, and liquid paraffin via oral gavage for 10 days. Results: Group 2 had significantly lower levels of glutathione peroxidase (GP-X) and superoxide dismutase (SOD) than group 1, but significantly greater levels of malondialdehyde (MDA). GP-X and SOD levels were significantly higher in mice given the doses of omega-369, and N-acetylcysteine prior to acetaminophen administration, whereas MDA levels were significantly lower in groups 3, 4, and 5 when compared with group 2. Conclusion: Omega-369 fatty acids, when taken orally, exhibit antioxidative effects and may reduce the risk of acetaminophen-induced liver injury.

Protective effect of nanoparticle NLRP3 inhibitor (MCC950) on cranial nerves in rats with vascular cognitive impairment

Background: Chronic cerebral hypoperfusion (CCH) is a common cause of Vascular cognitive impairment (VCI). The neuroinflammation caused by ischemia play a key role in the progression of the ailment process. The over activation of NLRP3/Caspase-1/IL-1β signaling aggravates the inflammatory response. We investigated whether NLRP3 inhibitors have a protective effect on cranial nerves in rats with VCI. Methods: Male SD rats were selected arbitrarily and categorized into the sham operation group, CCH group and CCH+MCC950 group (10 mg/kg). The rat model of CCH was formed by bilateral common carotid artery occlusion (BCCAO). The changes in rat’s cerebral blood flow were observed by laser speckle imaging after operation. The sham operation and the CCH group were given intraperitoneal (i.p) injection of normal saline, and the therapeutic group was given i.p having dose of MCC950 (10 mg/kg). The behavior of the rats was analyzed through the Y maze and open field experiments, and the hematoxylin-eosin (HE) staining technique was employed to analyze the behavior of the rats. The histological changes of the rat hippocampus were observed under the following conditions, cell apoptosis was observed by Tune staining, and the protein expressions of NLRP3, IL (interleukin)-1β, and cleaved-Caspase-1 in the hippocampus were analyzed by Western blot. Results: MCC950 treatment enhanced the working memory of CCH rats, and the rats in each group showed no motor deficit. As shown by HE staining, inhibition of NLRP3 reduced neuronal damage caused by pyroptosis. In addition, MCC950 diminishes the appearance of NLRP3, IL-1β, and cleaved-Caspase-1 in the brain tissue of CCH rats by inhibiting inflammasome formation. Conclusions: inhibitors can improve the learning and cognitive ability of rats with vascular cognitive impairment, and the mechanism might be linked to inhibiting the NLRP3/Caspase-1/IL-1β signaling and decreasing apoptosis.

Intra-Articular Facet Joint Injection of Normal Saline for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods: The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2467 potential studies, 3 were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1-1.5 months, and after 3-6 months, with MD and 95% CI of 2.43 and -11.61 to 16.50, -0.63 and -7.97 to 6.72, and 1.90 and -16.03 to 19.83, respectively, as well as on the quality of life after 1 and 6 months. Conclusions: The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP.

Melatonin Ameliorates Cyclophosphamide-Induced Spermatogenesis Disorder by Reducing Pyroptosis

As a chemotherapeutic drug, cyclophosphamide (CP) has a negative impact on male fertility due to its reproductive toxicity. Melatonin (Mel) promotes the male reproductive system and increases testosterone synthesis. This study is aimed at exploring the molecular mechanism of Mel as a protector of male fertility against CP-induced cytotoxicity. A CP toxicity model was established in adult ICR male mice by intraperitoneal injection of 100 mg/kg CP every other day for a week. Protective effects of Mel on the testis from CP-induced damage were evaluated using four groups of ICR male mice that received intraperitoneal injections of normal saline, 100 mg/kg CP, 10 mg/kg Mel, or the same dosage of CP and Mel, respectively. Testis morphology was observed by hematoxylin and eosin (HE) staining. Sperm quality parameters were evaluated, and sperm function was studied by in vitro fertilization (IVF). Proliferation, meiosis, and pyroptosis markers were examined by western blot. Results showed that CP treatment induced testis toxicity in a time-dependent manner with the most severe damage to the testis at two weeks post CP treatment. CP-treated mice showed reduced testicular weight and impaired spermatogenesis by downregulating PCNA and SYCP3, reduced serum testosterone levels, decreased sperm counts and motility, increased seminiferous tubule vacuolization, and oxidative damage to spermatogenic cells. All these effects, apart from testicular weight, could be ameliorated by Mel administration. The IVF experiment revealed that CP treatment reduced the rates of sperm fertilization and blastocyst development, which were also enhanced by Mel. Mel-treated mice also showed increased expression of proliferation-associated protein PCNA and meiosis-associated proteins REC8, STRA8, and SYCP3, which were all reduced by CP. Furthermore, Mel inhibited the pyroptosis of spermatogenic cells by reducing GSDMD and IL18 expression. In conclusion, this study indicated that Mel might protect the testis from CP-induced DNA damage to germ cells through the alleviation of pyroptosis.

Effect of Ketorolac Tromethamine Combined With Remifentanil on Reducing Complications During the General Anesthesia Emergence

PurposeTo observe the effect of ketorolac tromethamine combined with remifentanil in sedation and analgesia during general anesthesia emergence and reducing general anesthesia complications. DesignThis is an experimental design. MethodsA total of 90 patients who underwent partial or total thyroidectomy in our hospital were selected and randomly divided into three groups with 30 cases in each group. Routine general anesthesia combined with endotracheal intubation was given for general anesthesia, and different treatments were administered when the skin was sutured. Group K: intravenous injection of ketorolac tromethamine 0.9 mg/kg, intravenous injection of normal saline 10 mL/h by micropump until awakening and extubation; R group: intravenous injection of normal saline 2 mL, micropump intravenous injection of remifentanil 0.1 mcg/kg/min until awakening and extubation; KR group: intravenous injection of ketorolac tromethamine 0.5 mg/kg, micropump intravenous injection remifentanil 0.05 mcg/kg/min until awakening and extubation. After the operation, all patients entered the postanesthesia care unit (PACU) for recovery, extubation, scoring. The incidence and condition of various complications were counted. FindingsThere was no significant difference in the general information or operation duration of the patients (P > .05). The types of general anesthesia induction drugs in each group were the same, and there was no significant difference in drug measurement (P > .05). The visual analogue scales of KR group were: 2.2 ± 0.6(T0) and 2.4 ± 0.9(T1), the Self-Rating Anxiety Scale scores of the KR groups were: 4.1 ± 0.6(T0), 3.7 ± 0.4(T1). Compared with the KR group, the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were increased (P < .05); the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were not significantly different (P > .05); at T2, there was no significant difference in visual analogue scale and Self-Rating Anxiety Scale scores among the three groups (P > .05). There was no significant difference in extubation time or PACU transfer time among the three groups (P > .05). The incidence of adverse reactions in KR group were: 3.3% (nausea), 3.3% (vomit), 0 (coughing and drowsiness). Compared with the KR group, the incidence of adverse reactions was higher in the K and R groups. ConclusionsKetorolac tromethamine combined with remifentanil can effectively relieve pain and sedation during general anesthesia recovery and reduce the incidence of complications related to general anesthesia recovery. At the same time, the application of ketorolac tromethamine can reduce the dosage of remifentanil and inhibit the occurrence of adverse reactions when used alone.

Tissue Inhibitor of Metalloproteinase 3 as a potential staging biomarker in hepatocellular carcinoma

Objective: To assess the potential role of tissue inhibitor of metalloproteinase 3 as a staging marker of hepatocellular carcinoma.Method: The experimental study was conducted at Faculty of Pharmacy, Kafrelsheikh University, Egypt, from December 2020 to March 2022 after approval from the Faculty of Pharmacy, Kafrelsheikh University, Egypt, and comprised male albino rats. The subjects were divided into 4 groups. The control group was administrated a single intraperitoneal injection of normal saline, while the other groups were generated post-induction of hepatocellular carcinoma. The induction was done by injecting rats intraperitoneally with a single dose of 200mg/kg diethyl nitrosamine, followed by the administration of 0.05% phenobarbital sodium in drinking water daily. Rats were euthanised at 8, 16 and 24 weeks after the injection to obtain three groups related to the 3 stages of hepatocellular carcinoma. Serum was used for measuring the alpha protein level. Liver homogenates were used for the assessmentof the hepatic tissue inhibitor of metalloproteinase 3 expression, B-cell lymphoma 2-associated X protein expression, and the hepatic content of matrix metalloproteinase -9 and cyclin D1. Data was analysed using Graph Prism 8.Results: Of the 24 rats with weight range 120-130g, 6(25%) were in each of the 4 groups. The relative protein and messenger ribonucleic acid tissue inhibitor of metalloproteinase 3 expressions were significantly decreased in the intervention groups compared to the control group, with more decline as the hepatocellular carcinoma stage increased. The matrix metalloproteinase -9 and cyclin D1 concentrations and the relative hepatic protein Ki67 expression were significantly raised in the intervention groups compared to the control group (p&lt;0.05). The relative expression of hepatic B-cell lymphoma 2-associated X protein was markedly decreased in the intervention groupscompared to the control group (p&lt;0.05).Conclusion: Tissue inhibitor of metalloproteinase 3 might be a promising diagnostic and staging biomarker in hepatocellular carcinoma.Keywords: Carcinoma, Hepatocellular, Neoplasms, Fetoproteins, Metalloproteinase, Cyclin, Antigen, Phenobarbital, Nitrosamines.

Effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis

BackgroundSevere acute pancreatitis is a potentially life-threatening disease. Despite being a common disorder, acute pancreatitis lacks a specific treatment. The present study aimed to examine the effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis.MethodsMale ICR mice were randomly divided into 4 groups (n = 6 per group). The control group received two intraperitoneal (i.p.) injections of normal saline as a vehicle control. The acute pancreatitis (AP) group received two i.p. injections of L-arginine 450 mg/100 g body weight. AP plus probiotics groups received L-arginine to induce acute pancreatitis as above. In the single-strain and mixed-strain groups, mice received 1 mL of Lactobacillus plantarum B7 1 × 108 CFU/mL and 1 mL of Lactobacillus rhamnosus L34 1 × 108 CFU/mL and Lactobacillus paracasei B13 1 × 108 CFU/mL by oral gavage, respectively for 6 days starting 3 days prior to the AP induction. All mice were sacrificed 72 h after L-arginine injection. Pancreatic tissue was obtained for histological evaluation and immunohistochemical studies for myeloperoxidase, whereas ileal tissue was used for immunohistochemical studies for occludin, and claudin-1. Blood samples were collected for amylase analysis.ResultsSerum amylase levels and pancreatic myeloperoxidase levels in the AP group were significantly higher than in controls and significantly decreased in probiotic groups compared with the AP group. Ileal occludin and claudin-1 levels were significantly lower in the AP group than in controls. Ileal occludin levels significantly increased, whereas ileal claudin-1 levels did not significantly change in both probiotic groups as compared with the AP group. The pancreatic histopathology showed significantly higher degree of inflammation, edema, and fat necrosis in the AP group, and these changes improved in mixed-strained probiotic groups.ConclusionsProbiotics, particularly the mixed-strain ones, attenuated AP via the reduction of inflammation and the maintenance of intestinal integrity.

The role of Botulinum toxin type A for prevention and treatment of cleft lip palate (CLP) post-operative scar: a systematic review

Background. Cleft lip palate (CLP) defects are the common orofacial defects found in newborns. The main treatment is lip and palate surgery, often resulting in a hypertrophic scar that significantly affects the patient's aesthetic appearance. Several studies showed the role of Botulinum toxin type A injections for prevention and treatment of CLP post-operative scarThis systematic review aims to review the role of Botulinum toxin type A for prevention and treatment of cleft lip palate surgery scar. Method. Online databases were searched for relevant studies from Google Scholar, PubMed and ProQuest. Data sources were searched using MeSH terms "botulinum toxin," "cleft lip palate," and "surgery scar" for all publications up to October 2022. All English papers regarding the role of Botulinum toxin type A in preventing and treating CLP post-operative scar were included. Papers not available in full text or English and not an experimental study were excluded. Result. Six studies are included in this systematic review consisting of three randomized controlled trials and three clinical studies. The experimental group received Botulinum toxin type A injections, while the control group received an injection of normal saline or other topical treatment. All of the included studies showed positive results regarding the role of Botulinum toxin type A marked with reduced scar width, good Vancouver Scar Scale (VSS), Visual Analogue Scale (VAS), patient satisfaction and no complications or side effects were found. Conclusion. The Botulinum toxin type A showed promising results for the prevention and treatment of CLP post-operative scar.

Melatonin alleviates ovarian function damage and oxidative stress induced by dexamethasone in the laying hens through FOXO1 signaling pathway

Oxidative stress can trigger follicular atresia, and decrease follicles quantity in each development stage, thereby alleviating reproductive activity. The induction of oxidative stress in chickens through intraperitoneal injection of dexamethasone is a reliable and stable method. Melatonin has been shown to mitigate oxidative stress in this model, but the underlying mechanism remains unclear. Therefore, this study aimed to investigate whether melatonin can recover aberrant antioxidant status induced by dexamethasone and the specific mechanism behind melatonin-dependent protection. A total of 150 healthy 40-wk-old Dawu Jinfeng laying hens with similar body weights and laying rates were randomly divided into three groups, with five replicates per group and 10 hens per replicate. The hens in the control group (NS) received intraperitoneal injections of normal saline for 30 d, the dexamethasone group (Dex+NS) received 20 mg/kg dose of dexamethasone for the first 15 d, followed by the 15 d of normal saline treatment. While in the melatonin group (Dex+Mel), dexamethasone (20 mg/kg dose) was injected intraperitoneally in the first 15 d, and melatonin (20 mg/kg/d) was injected in the last 15 d. The results showed that dexamethasone treatment significantly enhanced oxidative stress (P < 0.05), while melatonin not only inhibited the oxidative stress but also notably enhanced the antioxidant enzymes superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GSH-Px), and antioxidant genes CAT, superoxide dismutase 1 (SOD1), glutathione peroxidase 3 (GPX3), and recombinant peroxiredoxin 3(PRDX3) expression (P < 0.05). Melatonin treatment also markedly reduced 8-hydroxy deoxyguanosine(8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS) levels (P < 0.05) and apoptotic genes Caspase-3, Bim, and Bax in the follicle. In the Dex+Mel group, the Bcl-2 and SOD1 protein levels were also increased (P < 0.05). Melatonin inhibited the forkhead Box Protein O1(FOXO1) gene and its protein expression (P < 0.05). In general, this investigation revealed that melatonin might decrease oxidative stress and ROS by enhancing antioxidant enzymes and genes, activating the antiapoptotic genes, and inhibiting the FOXO1 pathway in laying hens.

Optogenetic activation of basal forebrain cholinergic neurons improves interval timing performance in rodents (P1-6.009)

<h3>Objective:</h3> To study the effect of basal forebrain optogenetic cholinergic activation in an interval timing task in freely behaving animals. <h3>Background:</h3> Cholinergic deficit is a major feature in patients with Alzheimer’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Parkinson’s and Alzheimer’s patients can have impairments in interval timing, or the ability to control movements in time. Timing is preserved across mammalian species, and timing tasks require subjects to estimate an interval of several seconds. These tasks require attention to time and working memory for temporal rules. Mice receiving scopolamine, a cholinergic inhibitor, perform poorly during timing tasks. Interval timing involves medial prefrontal cortical areas that receive prominent cholinergic input; our recent work showed that scopolamine impairs interval timing through disrupting stimulus-processing rather than temporal processing in the medial prefrontal cortex. However, it is unclear whether basal forebrain cholinergic neuron activation could improve timing performance. <h3>Design/Methods:</h3> ChAT-Cre transgenic mice were trained on a 12s interval timing task before bilateral basal forebrain stereotactic AAV-DIO-ChR2 injection and optic canulae implantation (AP −0.7, ML +/−1.8, DV AAV injection at −4.0 and −5.0, with optic canulae at −3.5). Laser (473nm) stimulation was assigned on/off randomly across trials, and interval timing tasks were performed 30 min after intraperitoneal scopolamine (1mg/kg) or normal saline injections. <h3>Results:</h3> Scopolamine induced interval-timing deficits were partially reversed by optogenetic activation of basal forebrain cholinergic neurons with 20Hz stimulation but not 4 Hz. <h3>Conclusions:</h3> Optogenetic activation of the basal forebrain cholinergic neurons improves interval timing performance. These data may have relevance for our understanding of cholinergic function in human diseases such as Parkinson’s disease and Alzheimer’s disease. <b>Disclosure:</b> Dr. Zhang has nothing to disclose. Mr. Kirkpatrick has nothing to disclose. Dr. Narayanan has nothing to disclose.

Lycopene attenuates D-galactose-induced cognitive decline by enhancing mitochondrial function and improving insulin signaling in the brains of female CD-1 mice

The incidence of neurodegenerative diseases is severely increasing with ageing. Lycopene (LYC), a carotenoid pigment, has been reported to have antioxidant, anti-inflammatory and neuroprotective properties. In the present study, we aimed to investigate the ameliorative effect of LYC on D-galactose (D-gal) induced cognitive defects and the underlying mechanisms. Forty-five female CD-1 mice (2 months old) were separated into three groups to be fed with either a normal diet or a LYC diet (0.03%, w/w, mixed into normal diet). Meanwhile, the mice were treated by intraperitoneal injection of normal saline or D-gal 150 mg/kg/day for 8 weeks. The behavioral test results indicated that LYC alleviated D-gal induced cognitive impairments. LYC ameliorated brain ageing by decreasing the number of SA-β-gal- stained neurons, downregulating the protein expression of the cellular senescence associated genes P19/P21/P53, increasing the activities of the antioxidant enzymes GSH and SOD, downregulating the level of ROS, inhibiting the activation of MAPKs signaling and downregulating the levels of the inflammatory cytokines IL-1β and TNFɑ in mouse brains. LYC ameliorated synaptic dysfunction by increasing the expression of the neurotrophic factor BDNF and synaptic proteins. Moreover, LYC attenuated D-gal-induced mitochondrial morphological damage, and promoted the expression of mitochondrial functional proteins. LYC also promoted insulin signal transduction in mouse brains through the regulation of IRS-1/AKT/GSK3β signaling.

Akt2 inhibitor promotes M2 macrophage polarization in rats with periapical inflammation by reducing miR-155-5p expression

To investigate the effect of Akt2 inhibitor on macrophage polarization in the periapical tissue in a rat model of periapical inflammation. Rat models of periapical inflammation were established in 28 normal SD rats by opening the pulp cavity of the mandibular first molars, followed by injection of normal saline and Akt2 inhibitor into the left and right medullary cavities, respectively. Four rats without any treatment served as the healthy control group. At 7, 14, 21 and 28 days after modeling, 7 rat models and 1 control rat were randomly selected for observation of inflammatory infiltration in the periapical tissues by X-ray and HE staining. Immunohistochemistry was used to detect the expression and localization of Akt2, macrophages and the inflammatory mediators. RT-PCR was performed to detect the mRNA expressions of Akt2, CD86, CD163, inflammatory mediators, miR-155-5p and C/EBPβ to analyze the changes in macrophage polarization. X-ray and HE staining showed that periapical inflammation was the most obvious at 21 days after modeling in the rats. Immunohistochemistry and RT-PCR showed that compared with those in the control rats, the expressions of Akt2, CD86, CD163, miR-155-5p, C/EBPβ, and IL-10 increased significantly in the rat models at 21 days (P < 0.05). Compared with saline treatment, treatment with the Akt2 inhibitor significantly decreased the expression levels of Akt2, CD86, miR-155-5p and IL-6 and the ratio of CD86+M1/CD163+M2 macrophages (P < 0.05) and increased the expression levels of CD163, C/EBPβ and IL-10 in the rat models (P < 0.05). Inhibition of Akt2 can delay the progression of periapical inflammation in rats and promote M2 macrophage polarization in the periapical inflammatory microenvironment possibly by reducing miR-155-5p expression and activating the expression of C/EBPβ in the Akt signaling pathway.

Optimal dose of normal saline for confirming correct peripheral venous access with precordial Doppler ultrasonography in children

Precordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330).

LC-MS/MS quantification of ropivacaine and local analgesic and adverse effects of Long-acting Ropivacaine Injection based on pharmacokinetic-pharmacodynamic modelling in Bama minipigs

The local analgesic efficacy and adverse effects of a new Long-acting Ropivacaine formulation were examined based on pharmacokinetic-pharmacodynamic (PK-PD) modelling in Bama minipigs. 24 Bama minipigs, 12 males and 12 females, were randomly and equally divided into the following treatment groups: normal saline injection, drug vehicle injection, Long-acting Ropivacaine Injection and Ropivacaine Hydrochloride Injection. After routine disinfection, a skin incision about 3 cm long and 3 cm deep was produced in the leg of each pig, and mechanical withdrawal threshold (MWT) measured at various times pre- and post-injection as an index of analgesia against incision pain. Plasma ropivacaine concentrations were also measured at the same times using a novel liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method. Minipigs were sacrificed 24 h post-injection and hearts collected for drug concentration measurements by LC-MS/MS. The LC-MS/MS method demonstrated high sensitivity, linearity and precision. The Long-acting Ropivacaine formulation produced a longer analgesic effect (∼12 h) at a lower plasma concentration than Ropivacaine Hydrochloride (∼4h), suggesting a better side-effects profile. A PK-PD model revealed a direct relationship between plasma ropivacaine concentration and MWT, with peak analgesia at about 1000 ng/mL and behaved good prediction ability. Long-acting Ropivacaine Injection is a superior local anaesthetic-analgesic treatment due to longer-lasting efficacy at lower concentrations compared to Ropivacaine Hydrochloride, which will reduce the risk of side effects such as cardiotoxicity.

Tissue Inhibitor Of Metalloproteinase 3 As A Potential Staging Biomarker In Hepatocellular Carcinoma.

To assessthe potential role of tissue inhibitor of metalloproteinase 3 as a staging marker of hepatocellular carcinoma. The experimental study was conducted at Faculty of Pharmacy, Kafrelsheikh University, Egypt, from December 2020 to March 2022 after approval from the Faculty of Pharmacy, Kafrelsheikh University, Egypt, and comprised male albino rats. The subjects were divided into 4 groups. The control group was administrated a single intraperitoneal injection of normal saline, while the other groups were generated post-induction of hepatocellular carcinoma. The induction was done by injecting rats intraperitoneally with a single dose of 200mg/kg diethyl nitrosamine, followed by the administration of 0.05% phenobarbital sodium in drinking water daily. Rats were euthanised at 8, 16 and 24 weeks after the injection to obtain three groups related to the 3 stages of hepatocellular carcinoma. Serum was used for measuring the alpha protein level. Liver homogenates were used for the assessment of the hepatic tissue inhibitor of metalloproteinase 3 expression, B-cell lymphoma 2-associated X protein expression, and the hepatic content of matrix metalloproteinase -9 and cyclin D1. Data was analysed using Graph Prism 8. Of the 24 rats with weight range 120-130g, 6(25%) were in each of the 4 groups. The relative protein and messenger ribonucleic acid tissue inhibitor of metalloproteinase 3 expressions were significantly decreased in the intervention groups compared to the control group, with more decline as the hepatocellular carcinoma stage increased. The matrix metalloproteinase -9 and cyclin D1 concentrations and the relative hepatic protein Ki67 expression were significantly raised in the intervention groups compared to the control group (p<0.05). The relative expression of hepatic B-cell lymphoma 2-associated X protein was markedly decreased in the intervention groups compared to the control group (p<0.05). Tissue inhibitor of metalloproteinase 3 might be a promising diagnostic and staging biomarker in hepatocellular carcinoma.

The healing effects of thymoquinone on experimentally induced traumatic tendinopathy in rabbits

ObjectivesThymoquinone is a major bioactive compound present in the black seeds of the Nigella sativa. Tendon injuries are almost 50% of all musculoskeletal injuries. The recovery of tendon after surgery has become a significant challenge in orthopedics.DesignThe purpose of this study was to investigate the healing effect of thymoquinone injections in 40 New Zealand rabbits tendon traumatic models.Materials and methodsTendinopathy was induced by trauma using surgical forceps on the Achilles tendon. Animals were randomly divided into 4 groups: (1) normal saline injection (control), (2) DMSO injection, (3) thymoquinone 5% w/w injection, and (4) thymoquinone 10% w/w injection. Forty-two days after surgery, biochemical and histopathological evaluations were done, and biomechanical evaluation was conducted 70 days after surgery.ResultsBreakpoint and yield points in treatment groups were significantly higher compared to control and DMSO groups. Hydroxyproline content in the 10% thymoquinone receiving group was higher than all groups. Edema and hemorrhage in the histopathological evaluation were significantly lower in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control and DMSO groups. Collagen fibers, collagen fibers with fibrocytes, and collagen fibers with fibroblasts were significantly higher in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control groups.ConclusionsThymoquinone injection in the tendon in the concentration of 10% w/w is a simple and low-cost healing agent that could enhance mechanical and collagen synthesis in traumatic tendinopathy models in rabbit.

Administration of a new nano delivery system coated with Tirofiban to prevent early thrombosis of vein graft.

To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function.