Rhodomyrtus tomentosa as a new anticancer molecular strategy in breast histology via Her2, IL33, EGFR, and MUC1.

The prevalence of breast cancer among patients in Indonesia is significant. Indonesian individuals maintain the belief that cancer cannot be cured alone by pharmaceuticals and treatment; herbal remedies must be used in conjunction. Rhodomyrtus tomentosa, also known as Haramonting, is an indigenous Indonesian medicinal plant renowned for its copious antioxidant properties. The objective of study was to assess the impact of haramonting on breast cancer by examining the expression of various biomarker proteins associated with breast cancer. Haramonting was administered to breast cancer model mice at different doses over a period of 30 days. Subsequently, blood and breast samples were obtained for immunohistochemistry and enzyme-linked immunosorbent assays (ELISA). Authors have discovered that there has been a notable rise in the proliferation of epithelial cells in the duct lobes, resulting in the formation of ducts and lobules. Additionally, the researchers discovered that the breasts exhibited distinct clinical and histological alterations. Haramonting possesses the capacity to restore the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) to normal levels in the blood serum of rats afflicted with cancer. The histopathological analysis of the breast tissue revealed elevated levels of Her2, IL33, EGFR, and MUC1. The authors also discovered a notable increase in the growth of epithelial cells, with two or more layers of cells reaching towards the centre of the duct. The size of the epithelial cells exhibits variability; however, this state ameliorates with the administration of a dosage of 300 mg/kgBW of this botanical specimen. This study proposes that Haramonting may be effective in treating breast cancer.

Rhodomyrtus tomentosa (Aiton) Hassk. (haramonting) protects against allethrin-exposed pulmo damage in rats: mechanistic interleukins.

Inhaling Allethrin (C19H26O3) may induce oxidative stress in lung cells by causing the formation of free radi-cals. Interleukins (IL) are a group of secreted cytokines or proteins and signaling molecules initially produced as an immune response by leukocytes. Rhodomyrtus tomentosa (Aiton) Hassk. (haramonting) contains antioxidants that may prevent lung damage induced by allethrin-containing electric mosquito repellents. In this study, six groups of rats were exposed to allethrin via an electric mosquito repellent, including positive, negative, and comparison control groups and three groups were administered Rhodomyrtus tomentosa (Aiton) Hassk at 100 mg/kg BW, 200 mg/kg BW, and 300 mg/kg BW. After 30 days, the pulmonary tissue and the blood were taken for immunohisto-chemical and ELISA analysis. The accumulation of inflammatory cells causes the thickening of the alveolar wall structures. Injuries were more prevalent in the A+ group than in the other groups. The connection between the alveoli and blood capillaries, which can interfere with alveolar gas exchange, is not regulated, and the lu-minal morphology is aberrant, causing damage to the alveolar epithelial cells. Exposure to electric mosquito coils containing allethrin can increase the expression of interleukin-1, interleukin-8, interleukin-9, and interleu-kin-18 in blood serum and tissues while decreasing the expression of interleukin-6 and interleukin-10. Like the Vitamin C group, Rhodomyrtus tomentosa can increase alveolar histological alterations by decreasing the ex-pression of IL-1ß, IL-8, IL-9, and IL-18 while increasing IL-6 and IL-10. So that this plant can be developed in the future as a drug to prevent lung harm from exposure.

The Effect of Secreted IL-10 from Mesenchymal Stem Cell on Immune Checkpoint Molecules.

Background: Immunosuppression in sepsis is hypothesized to result from the increased expression of the immune checkpoint molecules programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). PD-1 and PD-L1 blockade therapies have been reported to increase survival in septic animals. Currently, the interleukin (IL)-10 within mesenchymal stem cell (MSC) secretome is known for its immunomodulatory capacity. Objective: To study the effect of IL-10 within MSC secretome on the expression of immune checkpoints in the rat model of sepsis. Methods: We used 48 male Rattus norvegicus rats in this research and divided them into four groups: sham (rats without sepsis induction and treatment), control (sepsis-induced rats without treatment), T1 (sepsis-induced rats treated with 150 µL of secreted IL-10 from MSC), and T2 (sepsis-induced rats treated with 300 µL of secreted IL-10 from MSC). Forty-eight hours after sepsis induction, we terminated the rats and collected the blood to examine the PD-1 and PD-L1 expression levels. Results: We found a decrease in the relative expression of PD-1 in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group, but the decrease was not significant. We also found a decrease in the relative expression of PD-L1 mRNA in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group. Conclusion: Administering secreted IL-10 from MSC reduces the expression of PD-1 and PD-L1 in sepsis. These findings suggest that MSC secretome can improve the immunosuppression in sepsis.

Effect of Phaleria Macrocarpa (Scheff.) Boerl Leaf Ethanol Extract on Serum IL-6 and TNF-α Levels in Diabetic Rats.

Background: Hyperglycemia conditions in diabetes mellitus (DM) can turn on pro-inflammatory cytokines like IL-6 and TNF-α. These cytokines play a role in insulin resistance and the development of DM complications. People in Indonesia have used Phaleria macrocarpa to treat diabetes, but the leaf of this plant has not been studied to see if it can reduce inflammation. Objective: This study aims to analyze the effect of ethanolic extract of Phaleria macrocarpa leaves (EEPML) in serum IL-6 and TNF-α levels of diabetic rats. Methods: This study was an experiment with a post-test-only control group design. Thirty 8-week-old male Wistar rats were used in the study. They were split into six groups: K1 was the normal control group; K2 was the DM control group; K3, K4, and K5 were given EEPML at doses of 125, 250, and 500 mg/KgBW; and K6 was given metformin 45 mg/KgBW orally once a day for 14 days. A high-fat diet and a 30 mg/KgBWi.p injection of streptozotocin were used to make the diabetic rat model. ELISA method for measuring serum IL-6 and TNF-α levels. The Kruskal-Wallis and the Mann-Whitney test were used to examine the differences between the groups. Results: There were significant differences between treatment groups in the mean levels of serum IL-6 (p=0.017), but there were no significant differences in the mean levels of serum TNF-α (p>0.05). Conclusion: Administration of Phaleria macrocarpa leaf ethanol extract 125 mg/KgBW reduced serum IL-6 levels but could not significantly reduce serum TNF-α levels in diabetic rats.

Anti Inflammatory Action of Allium Sativum Ethanol Extract to Prevent Lung Damage in Smoker Rat Model.

Background: Smoking is the leading cause of death in worldwide and is known as one of the risk factors in the development and pathogenesis of several diseases and most are respiratory and cardiovascular diseases. Secondhand smoke (SHS) exposure is associated with negative health consequences including respiratory tract infection, asthma, and cancer. One of the pathogenesis that has known to cause these diseases is inflammation. Garlic (Allium sativum) is a medicinal herb that contains Allicin and other active constituents that are known to have anti-inflammatory ability by suppressing the expression and production of proinflammatory cytokines that will cause inflammation. Objective: The aim of this study is; to analyze the anti-inflammatory action of Allium sativum ethanol extract to prevent lung damage in the smoker rat model. Methods: This is a case-control study with five groups of rats each group contains of three rats. The five groups were negative control (KN), 10 days (10d) smoker (K1), 20 days (20d) smoker (K2), 20d smoker treated with Allium sativum for 10 days (K3) and 20d smoker treated with Allium sativum for 20 days (K4). After 20 days all animals were sacrificed and histological preparation of lung organs was observed under a microscope with 100 dan 400 times magnification and then captured by photomicrograph for analyzed. Results: There were improvements in lung structure both in group K3 and K4 . there was a decrease of leucocytes and inflammatory cells infiltration that covered almost all alveolar surface to 10-20% surface area and the dilated alveoli decrease from more than 50% to less than 30% area. The bronchus was clean in both two groups compared to the groups that were not treated with Allium sativum. Conclusion: This study shows that Allium sativum ethanol extract has the ability to prevent lung damage in the smoker rat model.

The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.

In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 µL (T1) and 300 µL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan-Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan-Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 µL being more effective.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFß. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

Correction: Sari, M.I.; Ilyas, S. The Expression Levels and Concentrations of PD-1 and PD-L1 Proteins in Septic Patients: A Systematic Review. Diagnostics 2022, 12, 2004.

There was an error in the original publication [...].

Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model.

Background: Tuberculosis (TB) of the spine is a highly disruptive disease, especially in underdeveloped and developing countries. This condition requires standard TB treatment for 9-18 months, which increases patient risk of drug-resistant TB. Consequently, this raises the concern of adopting additional therapies to shorten the treatment duration, improve the efficacy of anti-TB drugs, and further decrease damage in the affected tissues and organs. Matrix metalloproteinase- (MMP-) 1 is a key regulator of the destruction of the extracellular matrix and associated proteins and is a new potential target for TB treatment research. In the present study, we investigated the effects of doxycycline as an MMP-1 inhibitor in patients with spondylitis TB. Methods: Seventy-two New Zealand white rabbits with spondylitis TB were divided into 12 different groups based on incubation period (2, 4, 6, and 8 weeks) and doxycycline administration (without, 1 mg/kg body weight (BW), and 5 mg/kg BW). We observed the course of infection through the blood concentration changes and immunohistochemical examination of MMP-1, in addition to BTA staining, culture, polymerase chain reaction (PCR), and histopathological examination. Results: Treatment with once daily 5 mg/kg BW doxycycline significantly improved the blood MMP-1 level (p < 0.05) compared with the placebo and 1 mg/kg BW doxycycline. A significantly reduced ongoing infection and a higher healing rate were demonstrated in rabbits with a higher doxycycline dose through BTA staining, culture, PCR, and histopathology. Various degrees of vertebral endplates, vertebral body, and intervertebral disc destruction were observed in 32 rabbits with positive histopathological findings, in addition to positive inflammatory cell infiltration, characterized by numerous lymphocytes, macrophages, and epithelial cells, as well as abundant granulation tissue and necrotic substances proximal to the inoculated vertebral area. Bone and intervertebral disc destructions were more apparent in the untreated rabbits. Conclusion: Our study demonstrated the potential of doxycycline as an adjunctive treatment in spondylitis TB. However, limitations remain regarding the differences in the pathogenesis and virulence of Mycobacterium tuberculosis between rabbit and human systems, sample size, and the dose-dependent effect of doxycycline. Further studies are needed to address these issues.

Bioactive bacterial cellulose wound dressings for burns with collagen in-situ and chitosan ex-situ impregnation.

Bacterial cellulose (BC) is a biopolymer that commonly used for wound dressings regarding to its high in-vitro and in-vivo biocompatibility. Moreover, the three-dimensional fibers in BC become an advantageous for bioactive wound dressing application as they serve as templates for impregnation other supportive materials. Chitosan and collagen are two of the materials that can be impregnated to optimize the BC properties for serve as wound dressing material. Collagen can help skin cells grow on the wound sites, where chitosan has anti-bacterial properties and can bind red blood cells. BC-based wound dressings were made by impregnating collagen via in-situ method followed by immersing chitosan via ex-situ method into BC fibers for 24 h. The intermolecular interactions of amine groups in the wound dressing were confirmed by FTIR. The XRD diffractogram showed wider peaks at 14.2°, 16.6°, and 22.4° due to the presence of collagen and chitosan molecules in the BC fibers. SEM images confirmed that chitosan and collagen could penetrate BC fibers well. Other tests, such as water content, porosity, antibacterial properties, and haemocompatibility, indicated that the wound dressing was non-hemolytic. In-vivo test indicated that BC/collagen/chitosan wound dressing supported the wound healing process on second degree burn.

Effect of Garlic Ethanol Extract Administration on Gluthatione Levels to Prevent Oxidative Stress in Smoker Rat Model.

Background: Sickle Garlic (Allium sativum L.) is known as a spice native to western Asia has a strong antioxidant effect and revealed it functions as an antioxidant by increasing ROS-capture activity, cellular antioxidants, SOD, CAT, and GSH levels in cells. Cigarette smoke is very dangerous because it can cause serious illness and death. Cigarette smoke is a major source of exogenous ROS because its particles are high in free radicals. Smoking is also related to a decrease in the body's natural antioxidant levels. Glutathione (GSH) synthesis and expression were found to increase initially and then decrease after being exposed to cigarette smoke. Objective: The aim of this study is; to analyze effect of garlic ethanol extract administration on gluthatione levels to prevent oxidative stress in smoker rat model. Methods: This was a case-control study with a control group design, with 15 healthy rats (Rattus norvegicus, sp.) divided into three groups, KN untreated animals (control), K1 animals exposed to cigarette smoke for 40 days (smoker), and K2 animals exposed to cigarette smoke for 40 days and treated with Allium sativum 0.1 g per day for 40 days (smoker and Allium sativum L.). After 40 days of treatment, all animals, including the control, were sacrificed with 30 mg/IP ketamine injections, and the blood plasma were taken for examination. Results: there were significant difference in glutathione levels between the treatment groups (K2) with the control group (KN) and the smokers group (K1) (p <0.05). Conclusion: garlic ethanol extract administration can increase gluthatione levels and prevent oxidative stress in smoker rat model.

The potential of Andaliman (Zanthoxylum acanthopodium DC) fruit as an ethanol extract for neuroprotection in aged model rat.

Objective: Dementia is a common aging-related neurodegenerative disease in the elderly worldwide. Alterations in neurogenesis and angiogenesis factors have been linked to cognitive impairment in neurological disorders. However, synthetic drugs to improve memory disorders have uncomfortable side effects. The purpose of this study is to explore the neuroprotective potential of the fruit ethanol extract of andaliman (Zanthoxylum acanthopodium DC) [Andaliman fruit ethanol extract (AEE)] on brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and spatial memory in rat models of aging. Materials and Methods: This study had an experimental design with AEE. The 4 groups were treated as follows: N (normal), M (served as positive control), P1 (AEE 150 mg/kg bw), and P2 (AEE 300 mg/kg BW) for 8 weeks. Aged model rats (M, P1, and P2) were obtained by inducing D-galactose (150 mg/kg bw). BDNF and VEGF expression were determined by RT-PCR, and spatial memory was assessed using the test of the Moris Water Maze (MWM). The Kruskal-Wallis and Mann-Whitney tests were used to assess the statistical analysis. Results: AEE had a tendency to increase BDNF in P2 compared to the normal group (1.98 versus 1). VEGF expression increased in P1 and P2 compared to the normal group (1.14 and 1.29 versus 1). AEE at a dose of 300 mg/kg bw significantly improved spatial memory (p = 0.026). Conclusion: For eight weeks, AEE at a dose of 300 mg/kg bw considerably increased the potential to enhance VEGF and BDNF expression as well as spatial memory.

Anti-Aging Activity of Andaliman (Zanthoxylum Acanthopodium DC) Fruit Ethanol Extract on Brain Weight and p16INK4a Expression of Hippocampus in Aging Model Rats.

Background: Physiological aging and due to oxidative stress in long term will have an impact on cellular response disorders, can caused aging of hippocampus and senility. Brain weight is known to decrease with age and p16INK4a as aging biomarkers have been investigated. Andaliman is one of typical herbal plants from North Sumatra has been widely used as an antioxidant, anti-inflammatory and anti-aging. Objective: This study was evaluated effect of andaliman (Zanthoxylum acanthopodium DC) fruit ethanol extract (AEE) on brain weight and p16INK4a expression in aging model rats. Methods: This study was carried out experimentally of 24 male wistar rats. The treatment group consisted of 4 groups; KN= negatif control (normal), KP= positif control (aging model rat), P1 and P2= aging model rat + AEE at dose 150 and 300mg/kgbw, respectively. The aging model rats were D-galactose-induced at dose of 150mg/kgbw for 8 weeks. Brain weigth were recorded by digital scales. p16INK4a expression using immunohistochemical methods. The data analysis with Anova test. Results: This study showed differences brain weight between groups (p=0.523). Brain weight in P1 (1.34±0,06) and P2 (1.30±0.09) tendency increased than KP (1.29±0.62). The p16INK4a expression between groups significant difference (p=0.041), continued with post hoc Least Significant Difference (LSD) showed p16INK4a expression in KN significant decreased than KP (p=0.027). Likewise, p16INK4a expression in P2 was significant decreased than KP (p=0.010). Conclusion: Andaliman ethanol extract at a dose 300mg/kgbw for 8 weeks was improved aging process caused D-galactose induced.

Analysis of Cytochrome c Expression on Liver Histology of Hepatitis Rats after Administration of Tin and Olive Leaf Ethanol Extract.

<b>Background and Objective:</b> Hepatitis is a liver illness caused by a viral infection, autoimmune conditions or the use of certain medicines. In molecular hepatitis treatment, cytochrome c can be used as a potential predictor of the severity of liver impairment. In Asia, particularly in Indonesia, antioxidant-rich plants include <i>Ficus</i> <i>carica</i> and <i>Olea europaea.</i> This study aimed to see what impact cytochrome c in hepatitis after these two botanicals were administered. <b>Materials and Methods:</b> Rats were grouped as follows: Normal rats with no additions or herbs (G₀), the physiological solution group (G₁), the intravenous administration of the quercetin-copper (II) (G₂), Olive leaf extract or OLE (300 mg kg¹ b.wt.) (G₃) and Tin leaf extract or TLE (100 mg kg¹ b.wt.) (G₄). For an animal model of hepatitis, the rats were given thioacetamide 280 mg kg¹ b.wt., 8 days later. The rats were dissected and blood and liver samples were collected for enzyme and immunohistochemistry examination. <b>Results:</b> Malondialdehyde (MDA), superoxide dismutase (SOD) and cytochrome c expression levels differed significantly (p<0.05) across treatment groups in rat's models of hepatitis. Hepatocytes first displayed symptoms of lipid degradation, inflammatory and necrosis cells. When administered quercetin and the two herbs, necrosis and inflammatory cells were reduced, demonstrating that OLE and TLE can enhance liver histology and lower cytochrome c expression in a mouse model of hepatitis. <b>Conclusion:</b> Administration of Olive leaf extract (OLE) and Tin leaf extract (TLE) can improve liver histology in hepatitis model rats while decreasing cytochrome c expression, which is a mechanism for hepatocyte cell death.

The Expression Levels and Concentrations of PD-1 and PD-L1 Proteins in Septic Patients: A Systematic Review.

Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.

Umbilical Cord-Derived Mesenchymal Stem Cells Improve TGF-ß, α-SMA and Collagen on Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

Background: A Erectile dysfunction (ED) is one of the well-known comorbidities in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells. UC-MSCs are multipotent cells that attract considerable interest due to immunoregulatory properties and might be a potential strategy to regulate and recover the functional cells and tissues, including tissue improvement in DMED. Objective: This study aims to determine the efficacy of UC-MSCs in improving the erectile function of DMED rats through analyzing the expression of TGF-ß, α-SMA, and collagen. Methods: Total number of 30 male Sprague-Dawley rats (6 to 8 weeks old) were randomly divided into four groups (negative control group, positive control group, T1 group, and T2 group). After 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin to induce DM. At 8 weeks after STZ injection, rats with DMED were identified by unresponsive erectile stimulation within 30 min. PC group received 500 µL; T1 rats treated with 500 µL PBS containing 1x106 UC-MSCs; T2 rats treated with 500 µL PBS containing 3x106 UC-MSCs. After MSCs treatment, the rats were sacrificed and the corpus cavernosum tissues were prepared for histological observations. Results: This study resulted in the administration of UC-MSCs could downregulate the expression of TGF-ß, α-SMA, and collagen leading to the improvement of DMED. Conclusion: UC-MSCs improve the expression of TGF-ß, α-SMA, and collagen on erectile dysfunction in streptozotocin-induced diabetic rats.

Rats' umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats.

Aim Allergic rhinitis (AR) is a heterogeneous condition that has been associated with inflammatory responses and is characterized by clinical typical symptoms of nasal itching, sneezing, watery discharge and congestion. Mesenchymal stem cells (MSCs) are multipotent stem cells that have the immunoregulatory ability by secreting various cytokines which potent as a promising therapeutic modality for allergic airway diseases, including AR. The aim of this study was to investigate the effect of rat UC-MSCs on the number of mast cells, the expression of Hsp70 indicated by the nasal symptoms allergic, particularly nasal rubbing in ovalbumininduced AR rats. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and OVA+MSCs group). OVA nasal challenge was conducted daily from day 15 to 21, and UC-MSCs (1x106 ) were administrated intraperitoneally to OVA-sensitized rats on day 21. Nasal rubbing was observed from day 22 to 28. The rats were sacrificed on day 22 and day 28. The nasal cavity tissues were prepared for histological observations. Results The administration of UC-MSCs could reduce the number of mast cells and the expression of Hsp70 leading to reduction of nasal symptoms allergic, particularly nasal rubbing. Conclusion Based on this finding, MSCs present a promising immediate curative effect to the inflammatory reaction in AR rats.

Suppression of Wnt Expression by Increasing PI3K in Rats Cervical Carcinoma by Andaliman (Zanthoxylum acanthopodium).

<b>Background and Objective:</b> Cervical cancer is the leading cause of death for women in the world and Indonesia. This disease originates from a malignant tumour of squamous epithelial cells caused by infection with the Human Papilloma Virus (HPV). Antioxidants can reduce oxidative stress in and there are plants from Indonesia that have high antioxidants, namely andaliman (<i>Zanthoxylum acanthopodium</i>). This study aimed to analyze the role of andaliman on PI3K and Wnt signalling in cervical cancer histology. <b>Materials and Methods:</b> The study includes 5 treatments. The control group (K-), rats cancer model (K+), rats cancer model+the dose is 100 mg/b.wt. of ZAM (P₁), rats cancer model+the dose is 200 mg/b.wt. of ZAM (P₂) and rats cancer model+the dosage is 400 mg/b.wt. ZAM (P₃). On the 30th day after ZAM administration, the rats were dissected for the paraffin block and Wnt and PI3K immunohistochemical staining was prepared. <b>Results:</b> There was a significant difference between all groups (p<0.001) in Wnt and PI3K expression. The real role of ZAM in cervical cancer tissue was seen at the highest ZAM dose (P₃). Irregular mucosal folds and stretched interstitial connective tissue in the K+ group can return to regularity and improve at the P₃ dose. The administration of ZAM showed a significant difference in cervical tissue after benzopyrene injection. <b>Conclusion:</b> Andaliman (<i>Zanthoxylum acanthopodium</i>) extract increases PI3K expression through suppression of Wnt expression. It can be developed therapy molecularly to prevent cell growth into cancer.

Correlation of Myc Expression with Wee1 Expression by Zanthoxylum acanthopodium in Cervical Carcinoma Histology.

<b>Background and Objective:</b> Natural herbs and molecular therapy can be used to treat cervical cancer. The Myc and Wee1 control tumour cell fate and microenvironmental changes like angiogenesis activation and host immune response suppression. The study aims to know about the correlation of Myc and Wee1 expressions as a molecular therapy given by <i>Zanthoxylum acanthopodium</i>. <b>Materials and Methods:</b> There are five rat groups: Group K is the untreated group, Group K⁺ is the rats injected with benzopyrene, Group P₁ is the administration of <i>Zanthoxylum acanthopodium</i> 100 mg kg¹ b.wt., Group P₂ is the administration of <i>Zanthoxylum acanthopodium</i> 200 mg kg¹ b.wt. and Group P₃ is the administration of <i>Zanthoxylum acanthopodium</i> 400 mg kg¹ b.wt. The rats are dissected 30 days after receiving <i>Zanthoxylum acanthopodium</i>. To stain the cervical tissues, immunohistochemistry is performed. <b>Results:</b> <i>Zanthoxylum acanthopodium</i> administration caused epithelial thickening and decreased Myc expression in previously uncontrolled carcinomas from untreated malignancies, which now slowed and stopped growing into the normal epithelium. Wee1 expression revealed that this herb could repair tissue by drastically reducing Wee1 expression at a dose of 100-400 mg kg¹ b.wt. Similarly, at the highest dose, cervical carcinoma stops growing and the nucleus begins to form normally (p<0.01). <b>Conclusion:</b> The higher Myc expression on andaliman administration in cervical carcinoma decreases Wee1 expression in cervical carcinoma so these two proteins have a strong and significant correlation. <i>Zanthoxylum acanthopodium</i> can be administered at various dosages to lower the number of positive indexes of Myc and Wee1 expression in cervical carcinoma.

Analysis of Apoptotic Cells and Lung Inflammation after Given by Vitis gracilis.

<b>Background and Objective:</b> Herbs have the potential to be used in molecular therapy to treat inflammation and apoptosis. It has been demonstrated that the Indonesian native <i>Vitris gracilis</i> inhibits cytochrome c as a precursor to apoptosis. When body tissues are injured, infected with bacteria, exposed to toxins or exposed to heat that causes cell death, inflammation occurs. The current study aimed to look for the effect of <i>Vitis gracilis</i> extract in the lung histology of mice. <b>Materials and Methods:</b> Five treatment groups were used for the experiments, which were conducted inside the study. The T1 is the negative control, T2 is swimming mice with 0.2 mg kg¹ b.wt., of vitamin C, T3 is swimming mice with 50 mg kg¹ b.wt., of <i>Vitis gracilis</i>, T4 is swimming mice with 75 mg kg¹ b.wt., of <i>Vitis gracilis</i> and T5 is swimming mice with 100 mg kg¹ b.wt., of <i>Vitis gracilis</i>. The dislocation procedure was used to dissect mice, ketamine was administered before dissection and the lungs were removed for TUNEL assay examination. <b>Results:</b> There were no significant differences in inflammatory cells or index-positive apoptotic cells between the T1, T2 and T5 groups (p>0.05). The T3 group had the highest value, while the T1 group had the lowest. The highest dose of <i>Vitis gracilis</i> reduced lung cell inflammation while also improving histological structure, resulting in intact, nucleated and complete alveolar membranes with proportional endothelial cells. <b>Conclusion:</b> <i>Vitis gracilis</i> 100 mg kg¹ b.wt., can repair and reduce inflammation in lung tissue. As a result, the higher the dose of <i>Vitis gracilis</i>, the less cell apoptosis occurs in the lungs.