Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Promotes Liver Regeneration and Anti-Fibrotic Effect in Liver Fibrosis Animal Model.

<b>Background and Objective:</b> Liver fibrosis (LF) is a most common pathological process characterized by the activation of hepatocytes leading to the accumulation of extracellular matrix (ECM). Hypoxia precondition treated in MSCs (H-MSCs) could enhance their immunomodulatory and regeneration capability, through expressing robust anti-inflammatory cytokines and growth factors, known as H-MSCs secretome (SH-MSCs) that are critical for the improvement of liver fibrosis. However, the study regarding the efficacy and mechanism of action of SH-MSCs in ameliorating liver fibrosis is still inconclusive. In this study, the therapeutic potential and underlying mechanism for SH-MSCs in the treatment of liver fibrosis were investigated. <b>Materials and Methods:</b> A rat model with liver fibrosis induced by CCl₄ was created and maintained for 8 weeks. The rats received intravenous doses of SH-MSCs and secretome derived from normoxia MSCs (SN-MSCs), filtered using a tangential flow filtration (TFF) system with different molecular weight cut-off categories, both at a dosage of 0.5 mL. The ELISA assay was employed to examine the cytokines and growth factors present in both SH-MSCs and SN-MSCs. On the ninth day, the rats were euthanized and liver tissues were collected for subsequent histological examination and analysis of mRNA expression. <b>Results:</b> The ELISA test revealed that SH-MSCs exhibited higher levels of VEGF, PDGF, bFGF, IL-10, TGF-ß and IL-6 compared to SN-MSCs. <i>In vivo</i>, administration of SH-MSCs notably decreased mortality rates. It also demonstrated a reduction in liver fibrosis, collagen fiber areas, α-SMA positive staining and relative mRNA expression of TGF-ß. Conversely, SN-MSCs also contributed to liver fibrosis improvement, although SH-MSCs demonstrated more favorable outcomes. <b>Conclusion:</b> Current findings suggested that SH-MSCs could improve CCl₄-induced liver fibrosis and decrease α-SMA and TGF-ß expression.

Arctigenin, an anti-tumor agent; a cutting-edge topic and up-to-the-minute approach in cancer treatment.

Today, herbal-derived compounds are being increasingly studied in cancer treatment. Over the past decade, Arctigenin has been introduced as a bioactive dibenzylbutyrolactone lignan which is found in Chinese herbal medicines. In addition to anti-microbial, anti-inflammatory, immune-modulatory functions, Arctigenin has attracted growing attention due to its anti-tumor capabilities. It has been shown that Arctigenin can induce apoptosis and necrosis and abolish drug resistance in tumor cells by inducing apoptotic signaling pathways, caspases, cell cycle arrest, and the modulating proteasome. Moreover, Arctigenin mediates other anti-tumor functions through several mechanisms. It has been demonstrated that Arctigenin can act as an anti-inflammatory compound to inhibit inflammation in the tumor microenvironment. It also downregulates factors involved in tumor metastasis and angiogenesis, such as matrix metalloproteinases, N-cadherin, TGF-ß, and VEGF. Additionally, Arctigenin, through modulation of MAPK signaling pathways and stress-related proteins, is able to abolish tumor cell growth in nutrient-deprived conditions. Due to the limited solubility of Arctigenin in water, it is suggested that modification of this compound through amino acid esterification can improve its pharmacogenetic properties. Collectively, it is hoped that using Arctigenin or its derivates might introduce new chemotherapeutic approaches in future treatment.

A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions.

Non-Hodgkin's lymphoma (NHL) is a cancer that starts in the lymphatic system. In NHL, the important part of the immune system, a type of white blood cells called lymphocytes become cancerous. NHL subtypes include marginal zone lymphoma, small lymphocytic lymphoma, follicular lymphoma (FL), and lymphoplasmacytic lymphoma. The disease can emerge in either aggressive or indolent form. 5-year survival duration after diagnosis is poor among patients with aggressive/relapsing form of NHL. Therefore, it is necessary to understand the molecular mechanisms of pathogenesis involved in NHL establishment and progression. In the next step, we can develop innovative therapies for NHL based on our knowledge in signaling pathways, surface antigens, and tumor milieu of NHL. In the recent few decades, several treatment solutions of NHL mainly based on targeted/directed therapies have been evaluated. These approaches include B-cell receptor (BCR) signaling inhibitors, immunomodulatory agents, monoclonal antibodies (mAbs), epigenetic modulators, Bcl-2 inhibitors, checkpoint inhibitors, and T-cell therapy. In recent years, methods based on T cell immunotherapy have been considered as a novel promising anti-cancer strategy in the treatment of various types of cancers, and particularly in blood cancers. These methods could significantly increase the capacity of the immune system to induce durable anti-cancer responses in patients with chemotherapy-resistant lymphoma. One of the promising therapy methods involved in the triumph of immunotherapy is the chimeric antigen receptor (CAR) T cells with dramatically improved killing activity against tumor cells. The CAR-T cell-based anti-cancer therapy targeting a pan-B-cell marker, CD19 is recently approved by the US Food and Drug Administration (FDA) for the treatment of chemotherapy-resistant B-cell NHL. In this review, we will discuss the structure, molecular mechanisms, results of clinical trials, and the toxicity of CAR-T cell-based therapies. Also, we will criticize the clinical aspects, the treatment considerations, and the challenges and possible drawbacks of the application of CAR-T cells in the treatment of NHL.

The lethal internal face of the coronaviruses: Kidney tropism of the SARS, MERS, and COVID19 viruses.

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS-CoV-2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS-CoV and the SARS-CoV. According to several investigations, SARS-CoV causes proteinuria and renal impairment or failure. The SARS-CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS-CoV infection. And recently, during the 2019-nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.

Streptococcus Colonial Growth of Dental Plaque Inhibition Using Flavonoid Extract of Ants Nest (Myrmecodia pendans): An in Vitro Study

Objective: To know the activity of resistance of flavonoid content in ant nest plant in decreasing the number of colonies S. mutans oral cavity of children as a medic herbal material. Material and Methods: The subjects were plaque sample of 20 children aged 7-12 years. Research begins by making toothpaste from ant nest extract. Samples of children's dental plaque were inserted into BHIB media, after which incubated for 24 hours, 1/10 dilution with BHIB media three times, followed by TYC media planting and incubation of anaerob with temperature 370C for 48 hours. After that then count the number of colonies of S. mutans. Results: On ethyl acetate extract of ant nest incubated at room temperature with concentration 20%, 40%, 60%, 80%, 100% obtained a decrease from each treatment amount of Streptococcus mutans colony on TYC media with median value of each treatment was 89, 67, 64, 61, 59 and 51 for the ethyl acetate fraction, and 62, 61, 60, 59, 49 at the ethanol fraction. There was no significant difference between the six concentration groups (p>0.05). Conclusion: Flavonoids extract of ant nest plants have growth barrier on Streptococcus mutans bacteria, the greater the concentration given the greater the number of S. mutans colony.

Anti-Cancer and Anti-Proliferation Activity of Ethyl Asetat Extract From Ant Nest (Myrmecodia pendans) in Burkitt's Lymphoma Cancer Cells

Objective: To determine the activity of anti-cancer and anti-proliferation of ethyl acetate fraction of ant nest plants (Myrmecodia pendans) in Burkitt's Lymphoma cancer cells. Material and Methods: The study was conducted in a pure laboratory experimental method using Burkitt's Lymphoma cancer cell culture. Gradual research begins with the determination, extraction and fractionation of ant nest plants, to test for proliferation barriers. Data analysis using two-way ANOVA followed by Post Hoc LSD test with a significance level of 95%. Pearson correlation test was conducted. Results: The results of testing the inhibition of Burkitt's Lymphoma cell proliferation with ethyl acetate extract treatment showed that there was inhibition of cell growth based on the concentration given, starting from the lowest concentration of 15.625 µg/mL. Likewise, the incubation time factor of 24, 48, and 72 hours showed that the longer the incubation time, the greater the inhibition of cell growth. Antiproliferation analysis of flavonoid ethyl acetate extract based on concentration and incubation time on absorption of optical density Burkitt's Lymphoma was statistically significant (p = 0.00). Conclusion: Ant nest ethyl acetate extract has the effect of proliferation inhibition on Burkitt's lymphoma cells.

Nickel and Chromium Ion Levels in Hair and Gingival Crevicular Fluid with the Corrosion of Brackets in Orthodontic Patients: A Longitudinal Study

Objective: To assess the levels of nickel and chromium ions in hair and Gingival Crevicular Fluid (GCF) of orthodontic patients and to evaluate the corrosion of orthodontic bracket surfaces. Material and Methods: Nickel and chromium ion concentrations were measured in hair and GCF of 15 patients (9 females and 6 males, aged 16-28 years old) who had fixed orthodontic treatment using atomic absorption spectroscopy. The samples were taken before treatment (baseline), 4, 8, and 16 months later during treatment. Along with ionic sampling, microscopic sampling was done. One of each patient brackets was removed to get 15 brackets per group. Five brackets were taken randomly from each group to be examined under scanning electron microscope (SEM). Data obtained were analyzed using paired t-tests. Results: After 16 months, compared with the baseline, average hair nickel level changed from 0.125 µg/g to 0.956 µg/g with statistically significant difference (p=0.00); average chromium level changed from 0.090 µg/g to 0.295 µg/g but no significant difference (p>0.05); average GCF nickel level changed from 3.335 µg/g to 10.410 µg/g; average chromium level changed from 1.859 µg/g to 9.818 µg/g. Both of these increases were significant (p=0.000). SEM examinations showed that the corrosion on brackets was seen in the fourth month, and more severely visible after 8 and 16 months of uses. Conclusion: After 16 months of treatment, compared with the baseline, the hair nickel level was increased by 7.7 times; while for chromium was by 3.3 times. Gingival crevicular fluid nickel level was increased by 3.1 times and chromium level was by 5.3 times. The longer time of treatment, the more ions released and the more corrosion of brackets will be.

Analysis of Risk Factors of Biopsychosocial with Early Childhood Caries (ECC) in Indonesian Pre-School Children

Objective: To describe the Early Childhood Caries (ECC) in Indonesian preschool children based on biopsychosocial risk factors. Material and Methods: This research is an analytic observational with a cross sectional design toward 506 preschool children aged 2-6 years at East Luwu Regency, Indonesia. The biopsychosocial data studied were gender, ethnicity, personal hygiene, child psychology, age, nutritional status, and dental and oral health behavior. These data were obtained through a questionnaire and clinical examination (nutritional status). Multiple linear regression analysis was performed. The statistical tests were performed at the significance level of 0.05. Results: Characteristics of respondents based on parents' origin, found that the majority of respondents were parents from Bugis tribes (68.4%) with ECC frequency of 72.2%. Regarding the visit to the dentist, 12.6% were afraid of the dentist, with ECC frequency of 71.9%. Most children had normal nutritional status (67%) with ECC frequency of 69.3%. Biopsychosocial factors, which significantly affect the Early Childhood Caries, were parents' tribe (p=0.022) and age (p=0.011). There was an association between ECC with brushing teeth before going to bed (p=0.049), use of mouthwash (p=0.002) and consumption of snacks (p<0.001). Conclusion: Biopsychosocial factor indicators are affect the Early Childhood Caries towards Indonesian preschool children.

Pulse Rate Change After Childhood Anxiety Management with Modeling and Reinforcement Technique of Children's Dental Care

Objective: To know the influence of handling child anxiety with modeling and reinforcement technique on changes in pulse rate in dental and oral care. Material and Methods: The sample consisted of 53 children aged 6-12 years who first came to pedodontic clinic in dental and oral hospital education of Hasanuddin University. Anxiety level was measured using objective parameters, measurement of radial pulse. Measurement of anxiety level was done before and after modeling and reinforcement was given through three treatments: I: dental models; II: game and III: video modeling and reinforcement. Data analysis was done using the Kolmogorov-Smirnov test and Friedman test. Results: There was a decrease before and after modeling and reinforcement. Before intervention, the average pulse rates in treatment I, II and III were 90.79, 88.00 and 88.38, respectively. After intervention, the average decrease in pulse rate of five beats per minute seen in the first treatment (85.15), a decrease of seven beats per minute on the second treatment (81.98), while in treatment III the average decrease was eight beats per minute (80.19) (p<0.001). Conclusion: Modeling and reinforcement technique effectively reduces children's anxiety levels for dental and oral care.

Solution Inhibitory of Ant Nest (Myrmecodia Pendans) Extract on the Formation of Plaque in Children with Early Childhood Caries

Abstract Objective: To evaluate the effectiveness of gargling the solution of ant nest extract against plaque formation in children who experience Early Childhood Caries (ECC) when used as a mouthwash. Material and Methods: This study uses a pretest-posttest design with a control group. Thirty children with ECC, which were divided into three groups, namely the treatment group which was given a solution of extracts of ant nests concentrations of 5% and 10% and the control group gargling Aquades. Plaque scores were measured using the Greene and Vermillon method before and after the intervention. The paired t-test was used, with a significance level of 0.05 Results: Significant differences were found before and after the treatment of ant nest extract (r<0.05). The increase in OHI-S mean in the control group before treatment was 2.41 ± 0.72 and after treatment 2.53 ± 0.69 while in the treatment group there was a decrease in the OHI-S average in the group of 5% before treatment 2.66 ± 0.90 and after treatment 2.29 ± 0.95 and group concentration of 10% before treatment 2.51 ± 0.89 and after treatment 1.82 ± 0.75 Conclusion: The distribution of ant nest extract solution extract with the concentration of 5% and 10% would be more effective with ant nest concentration of 10% where it can inhibit dental plaque formation, and there is a significant difference in mean plaque scores between the control group and the treatment groups.

Comparison Between Nickel and Chromium Levels in Serum and Urine in Patients Treated with Fixed Orthodontic Appliances: A Longitudinal Study

Objective: To compare levels of nickel and chromium in serum and urine in orthodontic patients treated with fixed orthodontic appliances. Material and Methods: Nickel and chromium ion concentration were measured in serum and urine of twenty patients (12 females and 8 males, aged 17-28 years old) who had fixed orthodontic treatment using Coupled Plasma-Atomic Emission Spectroscopy. The samples were taken before treatment (Baseline), two months, and six months later during treatment. Data were analyzed using repeated ANOVA, Bonferroni post-hoc test, and paired t-tests. The level of significance was set at 5%. Results: Average serum nickel level changed from 6.420 ppb to 6.855 ppb. Average serum chromium level changed from 5.305 ppb to 5.505 ppb in 6 months. Average urinary nickel level changed from 5.320 ppb to 5.610 ppb. Average urinary chromium level changed from 5.370 ppb to 5.520 ppb in 6 months. There was a statistically significant difference in serum (p<0.001) and urinary chromium (p=0.007) levels between observation times. Conclusion: Orthodontic treatment might raise both urinary and serum nickel levels, but the differences were not statistically significant; the alterations in chromium levels were not consistent; nickel levels were higher in serum than in urine; chromium levels were higher in urine than in serum.

Characteristics Vertical Position of Mental Foramen Reviewed by Panoramic Radiography as a Guide in Predicting Individual's Age on Forensic Odontology Examination

Objective: To know the characteristics vertical position of mental foramen based on panoramic image as a guide in predicting the individual's age for the purposes of Forensic Odontology examination. Material and Methods: The method of this study was observational and descriptive by using the cross-sectional approach. The data is obtained from the secondary data, which is adopted by purposive sampling technique in RSGM FKG Hasanuddin University and RSUD Batara Guru Belopa, District Luwu, Indonesia. Data was analyzed by using descriptive analysis method. Results: Vertical position of mental foramen is mostly affected by age, but there are some cases where the Vertical position of mental foramen is not affected by the individual's age. Before the eruption processof permanent tooth finish, mental foramen is located closer with alveolar ridge. After the eruption process of permanent tooth, slowly mental foramen is moving halfway to the lower border of corpus mandible. As each individual grows older and resorption process occurs to alveolar bone, mental foramen will appear moving closer to alveolar ridge. Conclusion: The process of identifying mental foramen to predict individual's age in the relation with forensic odontology is possible to be done by using roentgen image in mandible of the dead victim. Although it still requires further identification, mental foramen position can be one of the references in predicting individual's age.

Determinant Factors of Dental Caries in Indonesian Children Age 8-12 Years

Objective: To evaluate the determinant factors of dental caries in Indonesian children aged 8-12 years. Material and Methods: This study was observational and analytical with a cross-sectional design. A total of 114 children were selected using simple random sampling technique. Primary data was obtained from a questionnaire about tooth brushing habits, the use of toothpaste containing fluoride and cariogenic eating habits and data of dental caries obtained from direct observed by a dentist. Univariat data were analyzed using descriptive and bivariate data were analyzed using Chi-square tests. Results: The results obtained by 44.8% fair category of children who have toothbrushing habits, use of toothpaste containing fluoride was 100%, and 71% middle category children who have cariogenic eating habits. The most consumed cariogenic food was ice cream with 76.3% participants consumed it one to three times a week. The most eaten cariogenic foods every day in this sample were syroup/pop ice soft drink (42.1%). No significant association between gender and dental caries incidence was observed (p>0.05). Conclusion: There is significant association between tooth brushing habits with dental caries in Indonesian children aged 8-12 years at primary school in district of East Luwu Regency Tomoni.