Mouse Foot Research Articles

Antiinflamation Activity Test of Keji Beling (Strobilanthes crispa (L.) Blume) Leaves Extraction on White Mencites (Mus musculus)

Background: Inflammation often occurs in According to data from WHO, 2004) the number of people with bone inflammation worldwide reached around 11.9 million people. In high-income countries, around 1.3 million people experience bone pain, while in low to middle-income countries, the prevalence reached 5.9 million. In Southeast Asia, there are 4.4 million people with arthritis. In North Sumatra, the prevalence of arthritis according to the diagnosis of health workers is 8.4%, while based on diagnosis or symptoms it reaches 19.2%. In Medan City, the prevalence based on the diagnosis of health workers is 5.1%, and based on diagnosis and symptoms it is 17.2%. The method used in this study is the formation of artificial edema on the soles of the feet of male white mice with 1% carrageenan induction. Testing the anti-inflammatory activity of keji beling leaf extract was carried out with 25 test animals divided into 5 treatment groups. The groups consisted of positive controls given sodium diclofenac at a dose of 6.5 mg/kgBW, negative controls given Na-CMC 0.5%, and three extract groups at doses of 100 mg/kgBW, 200 mg/kgBW, and 300 mg/kgBW. The results showed that the percentage of inflammation in the five test groups decreased consistently from the 60th minute to the 360th minute after carrageenan induction. The highest percentage of inflammation was recorded at the 120th minute for the Na-CMC group, followed by the 100 mg/kgBW, 200 mg/kgBW, 300 mg/kgBW, and sodium diclofenac groups. The highest percentage of inflammation inhibition was obtained from the sodium diclofenac portion, followed by 300 mg/kgBW, 200 mg/kgBW, and 100 mg/kgBW. This shows that the good inhibition percentage is owned by EDKB 300 mg/kgBW continued sodium diclofenac, and EDKB 200 mg/kgBW and 100 mg/kgBW. This indicates that the sodium diclofenac portion and extract with doses of 100, 200, and 300 mg/kgBW have the power to function as anti-inflammatory agents, compared to the Na-CMC group which showed no effect.

Characterization of Novel SARM1 Inhibitors for the Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Sterile α and Toll/IL-1 receptor motif-containing 1 (SARM1) is a central regulator of programmed axon death and a crucial nicotinamide adenine dinucleotide (NAD+) hydrolase (NADase) in mammalian tissues, hydrolyzing NAD+ and playing an important role in cellular NAD+ recycling. Abnormal SARM1 expression is linked to axon degeneration, which causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. In this study, we use PC6 assay of hydrolase activity, DRG axon regeneration and CIPN model to screen for potent SARM1 Inhibitors. Two novel SARM1 inhibitors (compound 174 and 331P1) are charcterized for its high potency for SARM1 NADase. In a chemotherapy-induced peripheral neuropathy (CIPN) myopathy model, compound 331P1 treatment prevented the decline in neurofilament light chain (NfL) levels caused by axonal injury in a dose-dependent manner, associated with elevated intraepidermal nerve fiber (IENF) intensity in mouse foot paw tissue, suggesting its functionality in reversing axon degeneration. The newly designed SARM1 inhibitor 331P1 is a promising candidate due to its excellent in vivo efficacy, favorable CYP inhibition properties, and attractive safety profiles. The 331P1 compound possesses the potential to be developed as a novel neuroprotective therapy that can prevent or halt the neurodegenerative process in CIPN.

Research on preventive effect of Akkermansia muciniphilaAKKPROBIO on acute gouty arthritis in mice.

In mice with acute gouty arthritis, this study intends to examine the mechanism of action of Akkermansia muciniphila AKK PROBIO. We developed a mouse model of acute gouty arthritis using sodium urate. The efficiency and mechanism of AKK PROBIO in preventing acute gouty arthritis in mice were then determined by examining the degree of foot swelling, pain threshold, blood biochemical indicators, histological alterations, and messenger RNA (mRNA) expression changes. The results of the animal experiment showed that AKK PROBIO can lessen mouse foot edema severity and increase pain threshold. AKK PROBIO can enhance the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) in the ankle joint tissues of mice with acute arthritis while decreasing the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA). Interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels are all reduced by AKK PROBIO in the blood of mice with acute arthritis. Results from histopathology showed that AKK PROBIO reduced tissue damage in the mouse ankle and foot joints. In the tissues of the ankle joints of mice with acute arthritis, the results of the quantitative polymerase chain reaction (qPCR) and Western blot experiments suggested that AKK PROBIO may inhibit the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the tissues. AKK PROBIO can also regulate gut microbiota, inhibit harmful bacteria, and enhance valeric acid in the intestine, isobutyric acid, and isovaleric acid. Therefore, it is evident that AKK PROBIO prevents acute gouty arthritis better than glucosamine sulfate. It is a strain that has probiotic potential.

Involvement of TRPV4 in temperature-dependent perspiration in mice.

Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca2+ increases that were inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deficient mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with acquired idiopathic generalized anhidrosis (AIGA) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targeted to develop agents that regulate perspiration.

A study on the antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activity of the Artemisia vulgaris L. extract and its fractions

Ethnopharmacological relevanceVietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. Aim of the studyThe study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. MethodsAccording to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. ResultsThe assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 μM). ConclusionThe results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.

Preventive effects of Chinese Xinjiang naturally fermented yogurt separated from Lactobacillus rhamnosusAFY02 on acute gouty arthritis in mice.

Lactobacillus rhamnosus AFY02 (LR-AFY02) is a newly discovered strain isolated and identified from naturally fermented yogurt in Xinjiang, China. This research aims to investigate the mechanism of action of LR-AFY02 in mice with acute gouty arthritis. We examined the degree of foot swelling, pain threshold, blood biochemical indicators, histopathological changes, and mRNA expression. LR-AFY02 can decrease the severity of mouse foot edema and raise the pain threshold. LR-AFY02 can increase the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) while lowering the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA) in mice with acute arthritis. Interleukin-6 (IL-6), IL-10, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels in the blood of mice with acute arthritis are also decreased by LR-AFY02. Histopathological findings demonstrated that LR-AFY02 reduced tissue damage in the mouse foot and ankle joints. LR-AFY02 may suppress the mRNA expression of extracellular signal-regulated kinase 1/2 (ERK1/2), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), IL-6, interferon gamma (IFN-γ), and TNF-α in the tissues of the ankle joints of mice with acute arthritis. Additionally, LR-AFY02 has the ability to increase the expression of catalase (CAT), manganese superoxide dismutase (Mn-SOD), and copper/zinc superoxide dismutase (Cu/Zn-SOD). As a result, it is clear that L. rhamnosus AFY02 is more effective than glucosamine sulfate at preventing acute gouty arthritis.

Anti-inflammatory Property of Ethanolic Extract of Cleome spinosa Leaves in an in vivo Model of Delayed-type Hypersensitivity

Objectives Delayed-type hypersensitivity (DTH) reactions represent a clinically important class of immune responses that have wide-ranging implications in various health and disease conditions. The existing anti-inflammatory drugs to treat DTH have several shortcomings including severe side-effects. Thus, a new plant-derived anti-inflammatory drug with no or less toxicity would be effective in treating DTH. The Cleome genus has been routinely used to cure various ailments including inflammation. This study investigates the anti-inflammatory properties of the ethanolic leaf extract of Cleome spinosa (CSE) in a DTH model for the first time. Materials and Methods DTH response was induced by 2, 4-di nitro-fluorobenzene in the mouse foot pad. Histological sectioning of the paw was carried out to find changes in the architecture of the tissue. Serum tumour necrosis factor-alpha (TNF-α) was estimated through enzyme linked immunosorbent assay (ELISA), and the bioactive compounds present in CSE were analysed through reversed phase-high-performance liquid chromatography. Results With CSE treatment, the oedema in the resensitized paw alleviated faster with no loss of digits compared to the controls. Histological study of the resensitized paw showed less dermal and sub-dermal thickening and less collagen deposition that regained normal tissue architecture during the healing process with CSE treatment. CSE treatment did not show any adverse haematological and histopathological changes in the visceral organs of mice. The level of serum TNF-α was found to be significantly lower with CSE treatment. CSE was found to be rich in phenol, flavonoids, tocopherol, carotene and phytosteroids. Conclusion The anti-inflammatory and immunomodulatory role of CSE against hapten-induced deleterious DTH inflammation suggests its therapeutic potential in treating inflammatory diseases and combating infections.

The Milk of Cows Immunized with Trivalent Inactivated Vaccines Provides Broad-Spectrum Passive Protection against Hand, Foot, and Mouth Disease in Neonatal Mice.

Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants.

Human Adipose-Derived Mesenchymal Stem Cells Colonize and Promote Healing of Leprosy Ulcer by Inducing Neuro-Vascularization.

Leprosy ulcer is a chronic and recurrent disease resulting from nerve injury. While existing treatments partially facilitate ulcer healing, they exhibit limited ability to address localized nerve repair, leading to a risk of recurrence. Moreover, there is a dearth of animal models to evaluate the preclinical efficacy and safety of novel therapeutic approaches. Over the years, adipose-derived mesenchymal stem cells have been extensively employed in regenerative medicine as an optimal cell therapy source for fostering skin ulcer healing. They have also demonstrated the capacity to enhance nerve regeneration in in vitro experiments and clinical trials. In this study, we established a NU/NU mouse foot pad leprosy ulcer model, transplanted human adipose-derived stem cells (hADSCs) into leprosy ulcers via local injection, and conducted subsequent follow-up. Our findings revealed that hADSCs persisted in the leprosy ulcer and facilitated the healing process. In this respect, gross observation and histological analysis revealed increased granular formation, collagen synthesis, and re-epithelialization in the local ulcer area. RNA-Seq data revealed that the upregulated differential genes resulting from the transplantation intervention were not only enriched in pathways related to re-epithelialization and collagen synthesis but also contributed to local nerve regeneration. Furthermore, immunofluorescence assays revealed the increased expression of angiogenesis markers-CD31 and VEGFa, cell proliferation markers-Ki67 and TGF-β, and nerve regeneration markers-β3-tubulin, SOX10, NGF, and NT-3. These results underscore the potential of hADSCs in promoting the healing of leprosy ulcers and offer valuable preclinical data for their prospective clinical application.

Two-dimensional time-resolved scintillating sheet monitoring of proton pencil beam scanning FLASH mouse irradiations.

Dosimetry in pre-clinical FLASH studies is essential for understanding the beam delivery conditions that trigger the FLASH effect. Resolving the spatial and temporal characteristics of proton pencil beam scanning (PBS) irradiations with ultra-high dose rates (UHDR) requires a detector with high spatial and temporal resolution. To implement a novel camera-based system for time-resolved two-dimensional (2D) monitoring and apply it in vivo during pre-clinical proton PBS mouse irradiations. Time-resolved 2D beam monitoring was performed with a scintillation imaging system consisting of a 1mm thick transparent scintillating sheet, imaged by a CMOS camera. The sheet was placed in a water bath perpendicular to a horizontal PBS proton beam axis. The scintillation light was reflected through a system of mirrors and captured by the camera with 500 frames per second (fps) for UHDR and 4 fps for conventional dose rates. The raw images were background subtracted, geometrically transformed, flat field corrected, and spatially filtered. The system was used for 2D spot and field profile measurements and compared to radiochromic films. Furthermore, spot positions were measured for UHDR irradiations. The measured spot positions were compared to the planned positions and the relative instantaneous dose rate to equivalent fiber-coupled point scintillator measurements. For in vivo application, the scintillating sheet was placed 1cm upstream the right hind leg of non-anaesthetized mice submerged in the water bath. The mouse leg and sheet were both placed in a 5cm wide spread-out Bragg peak formed from the mono-energetic proton beam by a 2D range modulator. The mouse leg position within the field was identified for both conventional and FLASH irradiations. For the conventional irradiations, the mouse foot position was tracked throughout the beam delivery, which took place through repainting. For FLASH irradiations, the delivered spot positions and relative instantaneous dose rate were measured. The pixel size was 0.1mm for all measurements. The spot and field profiles measured with the scintillating sheet agreed with radiochromic films within 0.4mm. The standard deviation between measured and planned spot positions was 0.26mm and 0.35mm in the horizontal and vertical direction, respectively. The measured relative instantaneous dose rate showed a linear relation with the fiber-coupled scintillator measurements. For in vivo use, the leg position within the field varied between mice, and leg movement up to 3mm was detected during the prolonged conventional irradiations. The scintillation imaging system allowed for monitoring of UHDR proton PBS delivery in vivo with 0.1mm pixel size and 2ms temporal resolution. The feasibility of instantaneous dose rate measurements was demonstrated, and the system was used for validation of the mouse leg position within the field.

Rapid and non-invasive detection of malaria parasites using near-infrared spectroscopy and machine learning.

Novel and highly sensitive point-of-care malaria diagnostic and surveillance tools that are rapid and affordable are urgently needed to support malaria control and elimination. We demonstrated the potential of near-infrared spectroscopy (NIRS) technique to detect malaria parasites both, in vitro, using dilutions of infected red blood cells obtained from Plasmodium falciparum cultures and in vivo, in mice infected with P. berghei using blood spotted on slides and non-invasively, by simply scanning various body areas (e.g., feet, groin and ears). The spectra were analysed using machine learning to develop predictive models for infection. Using NIRS spectra of in vitro cultures and machine learning algorithms, we successfully detected low densities (<10-7 parasites/μL) of P. falciparum parasites with a sensitivity of 96% (n = 1041), a specificity of 93% (n = 130) and an accuracy of 96% (n = 1171) and differentiated ring, trophozoite and schizont stages with an accuracy of 98% (n = 820). Furthermore, when the feet of mice infected with P. berghei with parasitaemia ≥3% were scanned non-invasively, the sensitivity and specificity of NIRS were 94% (n = 66) and 86% (n = 342), respectively. These data highlights the potential of NIRS technique as rapid, non-invasive and affordable tool for surveillance of malaria cases. Further work to determine the potential of NIRS to detect malaria in symptomatic and asymptomatic malaria cases in the field is recommended including its capacity to guide current malaria elimination strategies.

Naja naja snake venom-induced local toxicities in mice is by inflammasome activation

Snake bite envenomation causes tissue damage resulting in acute and chronic inflammatory responses. Inflammasome activation is one of the factors involved in tissue damage in a mouse model of snake envenomation. The present study examines the potency of Indian Big Four snake venoms in the activation of inflammasome and its role in local and systemic tissue toxicity. Among Indian Big Four snake venoms, Naja naja venom activated NLRP3 inflammasome in mouse macrophages. Activation of NLRP3 inflammasome was also observed in mouse foot paw and thigh muscle upon administration of N. naja venom. Intraperitoneal administration of N. naja venom cause systemic lung damage showed activation of NLRP3 inflammasome. Treatment with MCC950, a selective NLRP3 inflammasome inhibitor effectively inhibited N. naja venom-induced activation of caspase-1 and liberation of IL-1β in macrophages. In mice, MCC950 partially inhibited the activation of NLRP3 inflammasome in N. naja venom administered foot paw and thigh muscle. In conclusion, the present data showed that inflammasome is one of the host responses involved in N. naja snake venom-induced toxicities. The inhibition of inflammasome activation will provide new insight into better management of snake bite-induced local tissue damage.

Emodin inhibits HDAC6 mediated NLRP3 signaling and relieves chronic inflammatory pain in mice.

Chronic pain reduces the quality of life and ability to function of individuals suffering from it, making it a common public health problem. Neuroinflammation which is mediated by the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the spinal cord participates and modulates chronic pain. A chronic inflammatory pain mouse model was created in the current study by intraplantar injection of complete Freund's adjuvant (CFA) into C57BL/6J left foot of mice. Following CFA injection, the mice had enhanced pain sensitivities, decreased motor function, increased spinal inflammation and activated spinal astrocytes. Emodin (10 mg/kg) was administered intraperitoneally into the mice for 3 days. As a result, there were fewer spontaneous flinches, higher mechanical threshold values and greater latency to fall. Additionally, in the spinal cord, emodin administration reduced leukocyte infiltration level, downregulated protein level of IL-1β, lowered histone deacetylase (HDAC)6 and NLRP3 inflammasome activity and suppressed astrocytic activation. Emodin also binds to HDAC6 via four electrovalent bonds. In summary, emodin treatment blocked the HDAC6/NLRP3 inflammasome signaling, suppresses spinal inflammation and alleviates chronic inflammatory pain.

Altered Gait in Charcot Neuropathic Mice: A Kinematic Analysis

Category: Diabetes; Hindfoot Introduction/Purpose: Charcot arthropathy is known to cause neurodegenerative as well as physical skeletal changes that can affect gait. A verified model of inducing Charcot arthropathy in mouse hindlegs exists, but clinical data has yet to be gathered from this model. This is a pilot study with the purpose of gathering clinical data on mouse gait and joint reactive forces that occur over time as a result of Charcot arthropathy utilizing MatLab software. Methods: Eleven wild-type 25-week-old C57BL/6J were included in this study. Group A (n= 6) was fed a high-fat 60% kcal diet starting at the age of 6 weeks and underwent a verified running protocol to induce microtrauma leading to hind-paw Charcot-type arthropathy. Sensory testing and fasting blood glucose levels confirmed the presence of hyperglycemia and neuropathy in Group A. Group B (n= 5) was fed a normal diet and did not complete a running protocol. At week 0 and week 16 of the study, brightly colored dots were placed on mice hindlimbs to mark the hip, knee, ankle, and tarsal joints. The mice were placed on the treadmill at a constant speed of 10 m/sec and were recorded in slow motion for 2-3 full gait cycles. MATLAB was used to measure gait angles and coordinates in space by following the corresponding colored dot for each joint on the mouse (Figure 1). Results: The control mice did not have significant changes in range of motion of the knee, ankle, or midfoot while walking between weeks 0 and 16. In contrast, the mice fed a high-fat diet had statistically significant differences in ankle range of motion (p=0.0275), nearly significant differences in knee range of motion (p=0.0991), and insignificant differences in midfoot range of motion between weeks 0 and 16. In addition, the differences between range of motion of the knee of the control vs. C57BL/6J mice were significantly different between groups at both weeks 0 (p=0.0016) and 16 (p=0.0201). In the ankle, the difference was statistically significant at week 0 (p=0.0275) but not week 16 (p=0.7066), presumably due to a large standard deviation in ankle range of motion. Conclusion: Results of this gait analysis indicate that mice with Charcot-like arthropathic changes demonstrated gait differences that affected the range of motion of the knees and ankles of the mice, but not the midfoot. These changes could be due to the neuropathic abnormalities induced in mouse feet that would cause gait changes. Future studies will include a larger sample size of mice with gait analysis done at intermediate time points to further quantify how gait changes over time with Charcot arthropathy.

Uji Efektivitas Antiinflamasi Kombinasi Ekstrak Herba Seledri (Apium Graveolens L.) Dan Daun Binahong (Anredera Cordifolia (Ten.) Steenis) Pada Tikus Putih

Inflammation is a protective response that is intended to eliminate the initial cause cell injury and cell discard and necrotic tissue caused by cell damage. Plants suspected of having anti-inflammatory properties as is Herba Celery (Apium graveolens L.) which included family Apiaceae and leaves Binahong (Anredera cordifolia (Ten.) Steenis) are included in the family basellaceae. Which act as antiinflammatory herbs binahong celery and leaves are flavonoids. This study aims to determine the effect of anti-inflammatory herb extract combination Celery (Apium graveolens L.) and leaves Binahong (Anredera cordifolia (Ten.) Steenis) against a white male rats. Herbal extract and leaf celery binahong extracted using 96% ethanol by maceration method. Animal test used was a white male rats as much as 25 animals with body weight of 100-300 grams. The test animals were divided into 5 groups: negative control group (CMC 1%), the positive control group (Diclofenac Sodium 50 mg), group combination herbal extracts celery and leaves binahong with a dose of 200 mg / kg: 200 mg / kg, 100 mg / kg: 300 mg / kg, 300 mg, kg: 100 mg / kg. Treatment 1 hour before the feet of mice induced by subplantar karagenin on the rear left foot white male rats. Edema volume measurements on the soles of mice were observed every 1 hour for 5 hours. The results showed a combination of herbal extracts and leaf celery binahong show stable results, where the hour-3 increased volumes continued in the hours 4th and 5th. Results per cent udema on a combination of herbal extracts and leaf celery binahong ie 49.13%, 44.66% and 45.92%. The average volume is used to calculate the percent edema inflammation, inflammation percent results obtained to calculate the percent inhibition.

TLR4 activation by lysozyme induces pain without inflammation.

Mostly, pain has been studied in association with inflammation, until recent studies which indicate that during bacterial infections, pain mechanisms could be independent of the inflammation. Chronic pain can sustain long after the healing from the injury, even in the absence of any visible inflammation. However, the mechanism behind this is not known. We tested inflammation in lysozyme-injected mice foot paw. Interestingly, we observed no inflammation in mice foot paw. Yet, lysozyme injections induced pain in these mice. Lysozyme induces pain in a TLR4-dependent manner and TLR4 activation by its ligands such as LPS leads to inflammatory response. We compared the intracellular signaling of MyD88 and TRIF pathways upon TLR4 activation by lysozyme and LPS to understand the underlying mechanism behind the absence of an inflammatory response upon lysozyme treatment. We observed a TLR4 induced selective TRIF and not MyD88 pathway activation upon lysozyme treatment. This is unlike any other previously known endogenous TLR4 activators. A selective activation of TRIF pathway by lysozyme induces weak inflammatory cytokine response devoid of inflammation. However, lysozyme activates glutamate oxaloacetate transaminase-2 (GOT2) in neurons in a TRIF-dependent manner, resulting in enhanced glutamate response. We propose that this enhanced glutaminergic response could lead to neuronal activation resulting in pain sensation upon lysozyme injections. Collectively we identify that TLR4 activation by lysozyme can induce pain in absence of a significant inflammation. Also, unlike other known TLR4 endogenous activators, lysozyme does not activate MyD88 signaling. These findings uncover a mechanism of selective activation of TRIF pathway by TLR4. This selective TRIF activation induces pain with negligible inflammation, constituting a chronic pain homeostatic mechanism.

Antibacterial and anti-inflammatory activity of sesquiterpene lactones compounds extracted from Artemisia Herba Alba plan

The Artemisia Herba Alba plant, is widespread in Iraq and its municipal kind called Artemisia herba alba is used as anti-parasites and anti-bacterial agent, it also has effective against different kinds of infections, this activity returns to Sesquiterpene lactone compounds, which are the main product of the Artemisia Herba Alba oil. In this study, these compounds were extracted from the Artemisia Herba Alb plant. The effectiveness of five one-half concentrations (200,100,50,25,12.5) mg / ml, against five species of pathogenic bacterial isolates from urinary tract infections (UTI) cases were tested , The activity of Sesquiterpene lactone compounds was significant (P&lt;0.05) for highest concentration of 200 mg /ml against P. aeruginosa, while the activity was not significantly against K .pneumoniae ,S. pneumoniae ,S. pyogenes when it is compared with standard antibiotic which is used against these pathogenic bacteria. In this study the anti-inflammatory activity of Sesquiterpene lactone compounds which induced by injection of carrageenan at the feet of laboratory mice, we found that these compounds was significantly (P &lt;0.05) more active in reducing the inflammation caused by the injection of carrageenan but not those efficiency shown by the use of anti-inflammatory aspirin to reduce inflammation to the laboratory mice resulting from the injection of carrageenan.

Correction of serum prooncogenic cytokines and metastases by 5-hydroxypyrimidine derivatives and doxorubicin after removal of a primary tumor node in mice with the Lewis lung epidermoid carcinoma

The effect of a single injection of doxorubicin, 8-day administration of two 5-hydroxypyrimidine derivatives, SNK-411 (2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine), on metastases, lifespan and serum cytokines has been investigated in С57ВL/6 mice after removal of a primary tumor node of Lewis lung carcinoma (LLC). LLC cells (1×106) were injected in the footpad of right hind feet of mice in control and experimental groups; after 14 days of tumor development the hind feet with the tumor were amputated at the ankle level. One hour before the amputation mice received a single injection of doxorubicin (4 mg/kg) and 8-day therapy with the 5-hydroxypyrimidine derivatives started. SNK-578 monotherapy was performed at a dose of 10 mg/kg administered intraperitoneally (i.p.). SNK-411 was administered per os at a dose of 25 mg/kg. In the case of combined therapy mice also received a single injection of doxorubicin (4 mg/kg; i.p.). The metastasis inhibition index in mice-treated with SNK-411 and SNK-578 were 53.3% as compared with control mice (with removed tumor). The mice-treated with SNK-411, doxorubicin, and the combination SNK-578 + doxorubicin had lifespan increased by 60.2%, 53.9%, and 42.9%, respectively. A single injection of doxorubicin, the course administration of the 5-hydroxypyrimidine derivative alone and in combination with single injection of doxorubicin completely decreased serum levels of the prooncogenic Th2-cytokines IL-4, and IL-6 and significantly decreased the level of the Th2-cytokine IL-5. Administration of doxorubicin, SNK-411 and SNK-578 did not influence serum concentration of Th1-cytokine interferon gamma (IFN-γ). These data confirm our previous findings that administration of the compounds studied decreased concentrations of prooncogenic IL-4 and IL-6 in tumor-bearing mice with LLC and had no effect on concentrations of the Th1-cytokine IFN-γ.

Notch1 down-regulation in lineage-restricted niches is involved in the development of mouse eccrine sweat glands.

Eccrine sweat gland (SG) restrictedly exists in mouse foot pads indicating that mouse plantar dermis (PD) contains the SG lineage-restricted niches. However, it is still unclear how these niches can affect stem cell fate towards SG. In this study, we tried to find the key cues by which stem cells sense and interact with the SG lineage-specific niches both in vivo and in vitro. Firstly, we used transcriptomics RNA sequencing analysis to screen differentially expressed genes between SG cells and epidermal stem cells (ES), and used proteomic analysis to screen differentially expressed proteins between PD and dorsal dermis (DD). Notch1 was found differentially expressed in both gene and protein levels, and was closely related to SG morphogenesis based on Gene Ontology (GO) enrichment analysis. Secondly, the spatial-temporal changes of Notch1 during embryonic and post-natal development of SG were detected. Thirdly, mouse mesenchymal stem cells (MSCs) were introduced into SG-like cells in vitro in order to further verify the possible roles of Notch1. Results revealed that Notch1 was continuously down-regulated along with the process of SG morphogenesis in vivo, and also along with the process that MSCs differentiated into SG-like cells in vitro. Hence, we suggest that Notch1 possibly acts as with roles of "gatekeeper" during SG development and regulates the interactions between stem cells and the SG lineage-specific niches. This study might help for understanding mechanisms of embryonic SG organogenesis.

ANTI-INFLAMMATORY ACTIVITY OF PEGAGAN LEAVES (Centella asiatica (L.) Urban) EXTRACT CREAM

Background: Pegagan leaves (Centella asiatica (L.) Urban) is an herbal plant family of Apiaceae containing the active ingredients of the triterpenoid group glycosides (asiaticoside, Asiatic acid, madekasat acid, madikassosida) centelloside, flavonoids, and Asiatic acids. Inflammation is a complex reaction in tissues that involves a response to blood vessels and leukocytes. Objective: The purpose of this study was to find out the anti-inflammatory activity that occurs in the legs of mice in the form of preparation of pegagan extract cream (Centella asiatica (L.) Urban). Methods: Pegagan extract is done by the maceration method that uses ethanol 70%. Test animals used to squeak white males as much as 10 heads with a body weight of 20-30 grams. Animals test were divided into 5 treatment groups, namely the pegagan extract group with a dose of 2 g/kg BB; 4 g/kg BB; 6 g/kg BB, positive control (Betason cream 0.1%), and negative control (pegagan extract 2 g/kg BB). 1 hour before treatment of squeaky soles is inducted with a 1% carrageenan solution subplantarically. Results: Measurement of edema volume on the soles of the feet of mice is observed every 1 hour for 6 hours. The results showed that pegagan extract cream with a dose of 6 g / kg BB showed the maximum percentage of inhibition edema that is at the 6 hours with a result of 80,2%. The results of the data analysis of the percentage of inhibition of Centella asiatica extract from the treatment group Negative Control-Formula II and Negative Control-Formula III showed significant differences (p&lt;0.05). Conclusion: Pegagan leaves extract has an anti-inflammatory effect on the feet of mice.&#x0D; Keywords: Anti-inflammatory, Pegagan leaves, Centella asiatica (L.) Urban