Nanofibrous electrospun scaffold doped with hydroxyapatite derived from sand lobster shell (Panulirus homarus) for bone tissue engineering.

Healing of significant segmental bone defects remains a challenge, and various studies attempt to make materials that mimic bone structures and have biocompatibility, bioactivity, biodegradability, and osteoconductivity to native bone tissues. In this work, a nanofiber scaffold membrane of polyvinyl alcohol (PVA)/polyvinylpyrrolidone (PVP)/chitosan (CS) combined with hydroxyapatite (HAp) from sand lobster (SL; Panulirus homarus) shells, as a calcium source, was successfully synthesized to mimic the nanoscale extracellular matrix (ECM) in the native bone. The HAp from SL shells was synthesized by co-precipitation method with Ca/P of 1.67 and incorporated into the nanofiber membrane PVA/PVP/CS synthesized by the electrospinning method with varying concentrations, i.e. 0, 1, 3, and 5% (w/v). Based on the morphological and physicochemical analysis, the addition of HAp into the nanofiber successfully showed incorporation into the nanofiber with small agglomeration at HAp concentrations of 1, 3, and 5% (w/v). This led to a smaller fiber diameter with higher concentration of Hap, and incorporating HAp into the nanofiber could improve the mechanical properties of the nanofiber closer to the trabecula bone. Moreover, in general, swelling due to water absorption increases due to higher hydrophilicity at higher HAp concentrations and leads to the improvement of the degradation process and protein adsorption of the nanofiber. Biomineralization in a simulated body fluid (SBF) solution confirms that the HAp in the nanofiber increases bioactivity, and it can be seen that more apatite is formed during longer immersion in the SBF solution. The nanofiber PVA/PVP/CS HAp 5% has the most potential for osteoblast (MC3T3E1) cell viability after being incubated for 24 h, and it allowed the cell to attach and proliferate. Additionally, the higher HAp concentration in the nanofiber scaffold membrane can significantly promote the osteogenic differentiation of MC3T3E1 cells. Overall, the PVA/PVP/CS/HAp 5% nanofiber scaffold membrane has the most potential for bone tissue engineering.

Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research.

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed by the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The most severe clinical phenotypes commonly arise from exacerbation of immune response following the infection of alveolar epithelial cells localized at the pulmonary blood-air barrier. Preclinical rodent models do not adequately represent the essential genetic properties of the barrier, thus necessitating the use of humanized transgenic models. However, existing monolayer cell culture models have so far been unable to mimic the complex lung microenvironment. In this respect, air-liquid interface models, tissue engineered models, and organ-on-a-chip systems, which aim to better imitate the infection site microenvironment and microphysiology, are being developed to replace the commonly used monolayer cell culture models, and their use is becoming more widespread every day. On the contrary, studies on the development of nanoparticles (NPs) that mimic respiratory viruses, and those NPs used in therapy are progressing rapidly. The first part of this review describes in vitro models that mimic the blood-air barrier, the tissue interface that plays a central role in COVID-19 progression. In the second part of the review, NPs mimicking the virus and/or designed to carry therapeutic agents are explained and exemplified.

Porous scaffold hydroxyapatite from sand lobster shells (Panulirus homarus) using polyethylene oxide/chitosan as polymeric porogen for bone tissue engineering.

The hydroxyapatite (HAp; Ca10 (PO4 )6 (OH)2 )) has good biocompatibility, bioactivity, and osteoconductivity as a bone implant because the main inorganic mineral of human bone is HAp. The use of scaffold HAp from biogenic resources that contain high calcium and polymer as a pore forming agent to support bone growth is a longstanding area of interest. In this study, porous scaffolds based on HAp were synthesized from sand lobster (SL; Panulirus homarus) shells as a source of calcium using the porogen leaching method with polyethylene oxide (PEO) and chitosan (Chs) as polymeric porogen. The present study aims to synthesize HAp derived from SL shells and evaluate the effect variations of PEO on the physicochemical properties of the scaffold and cytotoxicity in cell viability assay. Briefly, the SL shell powder was calcinated with temperature variations of 600°C, 800°C, and 1000°C for 6 h. Based on the characterization, it was shown that 1000°C was the optimum calcination temperature for SL shells to synthesize HAp using the precipitation method. The characterization results of HAp using energy dispersive x-ray (EDX) revealed that the molar ratio of Ca/P was 1.67. The Fourier transform infrared (FTIR) and x-ray diffractometer (XRD) spectral patterns indicated that HAp had been successfully synthesized with minor ß-tricalcium phosphate (ß-TCP), a calcium phosphate with high biocompatibility. Porous scaffolds were synthesized by varying the concentration of PEO at 0, 5, 10, and 15 wt %. Physicochemical analysis revealed that a higher concentration of PEO affected decreased crystallinity and compressive strength, but on the other hand, the porosity and pore sizes increased. Based on the physicochemical analysis, the synthesized porous scaffold showed that HAp/PEO/Chs 15 wt % had the most potential as a scaffold for biomedical applications. MTT Assay, after 24 h incubation, revealed that the scaffold was safe for use at low concentrations on the MC3T3E1 osteoblast cells, with a percentage of cell viability of 83.23 ± 3.18% at 23.4375 µg/mL. Although the cell viability decreased at higher concentrations, the HAp/PEO/Chs 15 wt % scaffold was cytocompatible with the cells. Thus, in the present study, HAp/PEO/Chs 15 wt % was the best scaffold based on pore structure, chemical composition, mechanical and crystalographic properties and cell viability.

Lingual morphology of domesticated Asian small-clawed otters in Yogyakarta, Indonesia.

This study aimed to observe the lingual morphology of the domesticated Asian small-clawed otter, Aonyx cinereus (A. cinereus), from Yogyakarta, Indonesia. Six domesticated A. cinereus adults were obtained from a local otter breeder in Yogyakarta, with no regard to sex. The animals were acclimated to the laboratory for one day, following this, the animals underwent macroscopy identification and scanning electron microscopy (SEM) and light microscopy (LM) analysis. Macroscopically, the tongue of domesticated A. cinereus is divided into three parts: the apex, corpus, and radix. The apex is the shortest part and can move freely. A median groove is bent along the corpus. Typically, the radix contains circumvallate papillae and the epiglottic valleculae. The SEM and LM observations revealed that the lingual morphology of A. cinereus consisted of two types of papillae: mechanical papillae (horny filiform, leaf-like filiform, bifid filiform, trifid filiform, elongated leaf-like filiform, triangular filiform and conical papillae) and gustatory papillae (fungiform and circumvallate papillae). The lingual glands consisted of Weber's glands and von Ebner's glands secreting acid and neutral mucins. Collagen fibres are found in the lamina propria and muscular layer. In conclusion, the papillae of the Asian short-clawed otter have the same structure as those of other Mustelidae family members.

A Review of the GSTM1 Null Genotype Modifies the Association between Air Pollutant Exposure and Health Problems.

Air pollution is one of the significant environmental risks known as the cause of premature deaths. It has deleterious effects on human health, including deteriorating respiratory, cardiovascular, nervous, and endocrine functions. Exposure to air pollution stimulates reactive oxygen species (ROS) production in the body, which can further cause oxidative stress. Antioxidant enzymes, such as glutathione S-transferase mu 1 (GSTM1), are essential to prevent oxidative stress development by neutralizing excess oxidants. When the antioxidant enzyme function is lacking, ROS can accumulate and, thus, cause oxidative stress. Genetic variation studies from different countries show that GSTM1 null genotype dominates the GSTM1 genotype in the population. However, the impact of the GSTM1 null genotype in modifying the association between air pollution and health problem is not yet clear. This study will elaborate on GSTM1's null genotype role in modifying the relationship between air pollution and health problems.

Milk Fermented with Pediococcus acidilactici Strain BE Improves High Blood Glucose Levels and Pancreatic Beta-Cell Function in Diabetic Rats.

This study evaluated the effects of milk fermented with Pediococcus acidilactici strain BE and Pediococcus pentosaceus strain M103 on diabetes in rats (Rattus norvegicus). The bacteria were separately used as starter cultures for milk fermentation, and the products were then fed to diabetic rats for 15 days. Blood glucose levels, immunohistochemical and histological indicators, lipid profiles, and total lactic acid bacterium counts were evaluated before and after treatment. The administration of milk fermented with P. acidilactici strain BE reduced blood glucose levels from 410.27±51.60 to 304.07±9.88 mg/dL (p<0.05), similar to the effects of metformin (from 382.30±13.39 mg/dL to 253.33±40.66 mg/dL, p<0.05). Increased insulin production was observed in diabetic rats fed milk fermented with P. acidilactici strain BE concomitant with an increased number and percentage area of immunoreactive beta-cells. The structure of insulin-producing beta-cells was improved in diabetic rats fed milk fermented with P. acidilactici strain BE or metformin (insulin receptor substrate scores of 5.33±0.94 and 3.5±0.5, respectively). This suggests that the administration of milk fermented with P. acidilactici BE potentially reduces blood glucose levels and improves pancreatic beta-cell function in diabetic rats.

Synthesis, Characterization, and Application of 2-((3-(Chloromethyl)-benzoyl)oxy)benzoic Acid: A Review.

Salicylic acid (SA) derivate is well-known for its anti-inflammatory and analgesic activity through cyclooxygenase (COX)-inhibition. Previous studies pointed toward gastric toxicity induced by most salicylic acid derivative compounds, particularly acetylsalicylic acid (ASA). Despite the adverse effect, ASA is still used due to price affordability and additional advantages in preventing platelet aggregation. Recently, a novel salicylic acid derivative called 2-((3 (chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl) was introduced as a potential alternative compound to substitute ASA. Preliminary assessment results of COX-2 specificity, toxicity profile, analgesic, anti-inflammatory, and antiplatelet activity have made 3-CH2Cl a promising compound for "new" drug development. This review focuses on the discovery, potential activity, and benefits of 3-CH2Cl and the possible molecular mechanisms of its regulations in health and disease. Thus, this review may prove to be beneficial for the utilization of 3-CH2Cl as a potential alternative drug to substitute ASA.

Chitosan hydrogel nanoparticle enhance therapeutic effect of bovine umbilical mesenchymal stem cell conditioned medium on canine cognitive dysfunction or canine Alzheimer's like mediated by inhibition of neuronal apoptotic.

In treating brain diseases, such as canine cognitive dysfunction (CCD), most currently available potent drugs have weak therapeutic efficacy. One of the causes is the inability of the substance to reach the brain in therapeutic quantities. These pharmaceuticals lacked targeted mechanisms for drug delivery, coming about in an elevated drug concentration in imperative organs, which drove to drug harmfulness. In recent years, cell-free treatment (conditioned medium) determined from animal and human stem cells has provided new promise for treating brain diseases, as CM can stimulate the regeneration of neurons and prevent the inflammation and apoptotic of neurons caused by pathology or aging. On the other hand, it is well known that chitosan-hydrogel (CH) is a polymer derived from natural sources. It has been authorized for use in biomedical use because of its uncommon biodegradability, biocompatibility, and mucoadhesive properties. CH modification has been utilized to generate nanoparticles (NPs) for intranasal and intravenous brain targeting. NPs shown upgraded drug take-up to the brain with decreased side impacts due to their drawn out contact time with the nasal mucosa, surface charge, nanosize, and capacity to extend the tight intersections inside the mucosa. Due to the aforementioned distinctive characteristics, developing Chitosan Hydrogel Nanoparticles load with bovine umbilical mesenchymal stem cell conditioned medium is crucial as a new therapeutic strategy for CCD.

Development of mucosal vaccine delivery: an overview on the mucosal vaccines and their adjuvants.

Currently, mucosal infectious diseases are still a very high global health burden, but there are few effective vaccines to prevent mucosal-borne diseases. The development of mucosal vaccines requires the selection of appropriate antigens, delivery system strategies, and adjuvants to increase vaccine efficacy but limited studies have been conducted. The aim of this review is to describe the mucosal immune system, as well as the potential for the development of vaccines and mucosal adjuvants, and their challenges. The study was conducted by applying inclusion criteria for the articles, and a review was conducted by two readers with the agreement. It was known that mucosal vaccination is a potential route to be applied in future preventive efforts through vaccination. However, limited studies have been conducted so far and limited mucosal vaccination has been approved. New technological approaches such as material development involving nano- and micro-patterning are important to intensively open and investigate the potential area of development to provide better vaccination methods.

The combination of isomalto-oligosaccharides (IMO)-based dietary fiber and hypocaloric high-protein diet could improve the anthropometric profile and fasting plasma glucose of healthy adults: A repeated single-arm clinical trial.

Background and aims: Meals with high protein and fiber could reduce weight and improve diabetes risk factors. Isomalto-oligosaccharide (IMO), a form of dietary fiber, could induce the afferent signal that causes appetite suppression. However, the direct effect of fiber supplementation in the form of IMO combined with a high-protein diet (HPF) on those parameters is still unknown. This study aims to investigate the effect of HPF on anthropometric parameters and blood glucose regulation of healthy subjects. . Methods: Thirteen healthy subjects were given a hypocaloric high protein diet (HPD) mixed with their prepared meals for two weeks. Followed by the HPF diet for another two weeks. Their anthropometric parameters, such as body composition (total body weight, body fat percentage, and fat-free mass), BMI and waist circumference, and fasting plasma glucose, were measured. Results: Compared to pre-intervention, HPF could significantly (p ≤ 0.004) reduce the anthropometric parameters and fasting plasma glucose. Compared to HPD, HPF could significantly (p ≤ 0.005) reduce more total body weight, body fat percentage, and BMI. In addition, HPF could induce more satiety than HPD (higher VAS score). Conclusion: HPF could improve the subject's anthropometric parameters which is obviously beneficial in preventing the risk of developing diabetes.

Molecular identification of lactic acid bacteria SR6 strain and evaluation of its activity as an anticancer in T47D cell line.

Background and Aim: Breast cancer is the most common type of cancer in women because it attacks the productive age. Preliminary studies showed that lactic acid bacteria (LAB) strain SR6 from the Bali cattle colon has the potential to act as a superior probiotic. It is also assumed that its bacteriocin structure is specific and has a strong relationship with the specificity of the ligand and its biological activity at a receptor. Therefore, this study aims to assess the use of local LAB strains, which produce bacteriocins as anticancer agents, as well as to identify the bacteria as potent producers molecularly. Materials and Methods: The study was initiated by cultivating LAB SR6 strain from stock isolates on De Man, Rogosa, and Sharpe (Oxoid, CM 0369, England) broth media. It was then confirmed molecularly through analysis of the 16S ribosomal ribonucleic acid gene. Subsequently, its anticancer activity was tested by assessing the cytotoxic activity in T47D cell culture using the 3-(4, 5 dimetiltiazol-2-yl)-2.5-diphenyl tetrazolium bromide (Invitrogen M6494, US) method. Results: The results showed that the LAB strain SR6 was identified molecularly as Pediococcus pentosaceus. Furthermore, it had a toxic effect on T47D cells, which was indicated by the number of deaths after treatment with the extracellular protein of the strain, especially at the 50% total cell volume level. Conclusion: Based on the toxic effect of the strain on human T47D cells, the LAB SR6 isolate, which was identified as P. pentosaceus has the potential to be developed as a good anticancer drug against breast cancer. However, there is a need to carry out an integrated study to fully explore the suitability of bacteriocins as in vivo therapeutics against the disease completely.

Morphology of lingual papillae in the Javan mongoose (Herpestes javanicus) by scanning electron microscopy and light microscopy.

There are variations in the tongue papillae among species, including the size, number and type of papillae. There have been no studies describing the detailed tongue morphology of Javan mongoose (Herpestes javanicus). Therefore, we analysed the tongue and lingual structures of Javan mongoose (H. javanicus), using scanning electron microscopy and light microscopy. The tongue was covered by papillae and rough in appearance. We divided the tongue into three regions: the apex, corpus and radix of the tongue. The medioventral section of the tongue was characterized by the presence of a frenulum. We identified four types of papillae: filiform, fungiform, conical and vallate papillae. There were two subtypes of filiform papillae: leaf-like and conical. Both were seen on the apex, although leaf-like filiform papillae also extended to the corpus. Fungiform papillae had taste buds on their dorsal surfaces and were observed from the apex to the radix. Vallate papillae, three in numbers only occurred on the radix. Periodic acid-Schiff (PAS) staining showed minor lingual glands on the textus muscularis striatus syncytialis of the corpus and lateral radix, which we identified as Weber glands; we also observed von Ebner glands on this layer of the tongue. These anatomical features of the Javan mongoose tongue are broadly similar to those seen in other carnivores, with some specific differences, such as the number of vallate papillae.

In Vitro Neuroprotective Effect of the Bovine Umbilical Vein Endothelial Cell Conditioned Medium Mediated by Downregulation of IL-1ß, Caspase-3, and Caspase-9 Expression.

Mesenchymal stem cells (MSCs) and conditioned medium (CM) derived from human umbilical blood cord stem cells (HUBSC) are now being extensively utilized. Human umbilical vein endothelial cells (HUVECs) have the same ability as HUBSC as an option for autologous therapy. In addition, cell therapy using HUVECs may produce protective signals for cerebral vessels and promote neuronal survival after hypoxic-ischemic damage. HUVECs have the same anatomical and physiological structure as bovine umbilical vein endothelial cells (BUVECs). In this study, we aim to determine the ability of BUVEC-CM to reduce inflammation and apoptosis on in vitro neurodegeneration models (PC12 and SH-SY5Y cell lines). BUVEC-CM obtained from the third and fourth passages were analyzed using liquid chromatography-mass spectrometry (LC-MS) and high-resolution mass spectrometry (HR-MS), while the other part was used as a treatment for in vitro model neurodegeneration. The PC12 and SH-SY5Y cell lines were cultured and grouped into seven different treatments, including untreated cells. As the treatment group, cells were given TMT 10 µM in the presence of different doses of CM (25%, 50%, 75%, and 100%); as a control comparison of recent therapy, donepezil was used. In addition, cells with the administration of TMT 10 µM were run as a positive control. Cell viability assay (CCK-8) and enzyme-linked immunosorbent assay (ELISA) were performed to identify the viability and expression of interleukin-1ß (IL-1ß), caspase-3, and caspase-9 for both PC12 and SH-SY5Y cells. The results showed that BUVEC-CM could significantly reduce IL-1ß expression and downregulate caspase-3 and caspase-9, as well as when compared to the donepezil group. Taken together, these results indicate that BUVEC-CM can be used as a potential candidate for neuroprotective agents by reducing the activity of IL-1ß and the expression of caspase-9 and caspase-3 in PC12 and SH-SY5Y cells induced by TMT. However, further research still needs to be conducted.

Dataset of Phytochemical and secondary metabolite profiling of holy basil leaf (Ocimum sanctum Linn) ethanolic extract using spectrophotometry, thin layer chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance.

Holy basil (Ocimum sanctum Linn) or known also as "kemangi" in Indonesia is a plant commonly used as a herb in Asian countries. It is also medicinal with antipyretic, anti-inflammatory, anti-cancer, and neuroprotective properties. This dataset article provides broad screening of the phytochemical component of Ocimum sanctum ethanolic extract (EEOS) as well as a secondary metabolite profile of EEOS. Analyses were done qualitatively and quantitatively using a combination of spectrophotometer, thin layer chromatography, Fourier transform infrared spectroscopy (FTIR), and 1H-nuclear magnetic resonance (1H-NMR). Results showed that Ocimum sanctum ethanolic extract contains phytochemical compounds, including flavonoids, phenols, tannins, saponins, alkaloids, steroids, and terpenoids. In addition, a secondary metabolite was found and classified into metabolite groups including alcohol, amine, carboxylic acid, alkane, alkene, aldehyde, phenol, ether, sulfur, halogen, benzene, nitrogen, sterol, amino acid, carbohydrate, and nitrogen.

Pre-meal high-performance inulin supplementation reduce post-prandial glycaemic response in healthy subjects: A repeated single-arm clinical trial.

BACKGROUND AND AIMS: High-performance (HP) inulin, a dietary fiber consists of more than 10 fructose polymers, have been shown to reduce post-prandial glycaemic response (PPGR) and could prevent the occurrence of Type-2 diabetes mellitus (T2DM). Currently, there are no data on whether pre-meal HP inulin supplementation could decrease PPGR. METHODS: 8 healthy adults consumed 20 g of formula that contain 60.2% inulin (w/w) dissolved in water. Blood glucose was measured in fasted participants and at 30-120 min after starting to eat a prepared meal. This test was repeated every week with different supplement formulas. CONCLUSION: pre-meal HP Inulin formula supplementation could suppress the post-prandial glycaemic response.

Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy.

Umbilical cord blood (UCB) cells are an important source of mesenchymal stem cells (MSCs). It is known that the umbilical cord is rich in hematopoietic stem cells, which influenced research on ontogeny and transplantation (allogeneic transplantation). In recent years, stem cell research has emerged as an area of major interest due to its prospective applications in various aspects of both human and veterinary medicine. Moreover, it is known that the application of MSCs has several weaknesses. The use of these cells has limitations in terms of tumorigenesis effect, delivery, safety, and variability of therapeutic response, which led to the use of secretomes as an alternative to cell-free therapy. The main obstacle in its use is the availability of human UCB as an origin of MSCs and MSCs' secretomes, which are often difficult to obtain. Ethical issues regarding the use of stem cells based on human origin are another challenge, so an alternative is needed. Several studies have demonstrated that MSCs obtained from bovine umbilical cords have the same properties and express the same surface markers as MSCs obtained from human umbilical cords. Therefore, secretomes from MSCs derived from domestic animals (bovine) can possibly be used in human and veterinary medicine. This finding would contribute significantly to improve cell-free therapy. At present, the use of UCB MSCs derived from domestic animals, especially bovines, is very restricted, and only limited data about bovine UCB are available. Therefore, the aim of this review was to provide an updated overview of cell-free therapy and discuss the new possibilities introduced by the generation of this therapy derived from bovine umbilical MSCs as a promising tool in developing modern and efficient treatment strategies.

Identification of the Lingual Papillae in the sugar glider (Petaurus breviceps) by scanning electron microscopy and light microscopy.

A morphological description of the sugar glider's (Petaurus breviceps) tongue was obtained from five individual sugar gliders and analysed under a scanning electron microscope and a light microscope using four methods of staining. The tongue has a noticeably elongated structure with three regions: apex, corpus and radix. Transition to the corpus is indicated by the sulcus medianus linguae and the frenulum on its ventral surface. The dorsal tongue displayed a raised mucous membrane manifesting as a type of papillae. Filiform papillae were differentiated into two subtypes: brush-like papillae, with a short base splitting into 5-6 processes; and flower bud filiform papillae that are shorter and wider than the former, and divided into a single main process and 4-5 secondary processes. Fungiform papillae with 1-2 taste buds are interspersed between filiform papillae and absent on the radix. Conical papillae cover the lateral margin of the corpus and increase in size when closer to the radix. Vallate papillae-three in number-are arranged as a triangular structure, with the middle papillae pointing towards the root of the tongue. A continuous groove wrapped around each papilla with several taste buds is found on its lateral surface. Two of the vallate papillae are located symmetrically on each side and are much smaller than the most caudal middle vallate that is directed posteriorly. A positive reaction using separate staining with periodic acid-Schiff and Alcian blue (pH 2.5) showed Weber's glands and von Ebner's glands appearing beneath the papillae, mainly on the muscle layer of the radix. Different reactions to the stains indicated that Weber's gland contains sialomucin and/or sulfomucin, whereas von Ebner's gland consists of serous cells secreting glycogen and/or neutral mucin. The collagen structure was identified using Masson's trichrome stain in the two bottom layers of the tongue from the apex, decreasing gradually towards the radix.

Morphological characterization of Horsfield's treeshrew Tupaia javanica lingual papillae: Light microscopy and scanning electron microscopy studies.

The Horsfield's treeshrew (Tupaia javanica) is one of the shrews found on the island of Java that mainly feeds on fruits and occasionally insects. This shrew has an important role in the ecosystem as it spreads plant seeds and controls insects. To this day, there is no available knowledge about the structure of Horsfield's treeshrew's tongue. Therefore, the aim of this study was to provide data on the tongue structure of the Horsfield's treeshrew through two different methods. We investigated the tongue morphology and lingual papillae distribution of Tupaia javanica using 1) scanning electron microscopy (SEM) for microscopic structure and 2) histology for microscopic organization. Our macroscopic results revealed that the tongue of Tupaia javanica can be divided into three parts: apex, corpus and radix. The dorsal surface of the medial corpus is the median groove extending to the radix. Observation using SEM and light microscopy (LM) showed that the apex of the tongue bears three types of papillae: scale-like filiform, small filiform and fungiform. These are rosette filiform papillae, cornflower filiform papillae, conical papillae and fungiform papillae in the corpus. Meanwhile, the radix contains small filiform papillae, scale-like filiform papillae, vallate papillae, conical papillae and fungiform papillae. On the lateral posterior radix, Weber's gland reacts positively to PAS reaction. Taking together, our research shows that there are variations in the papillae on the tongue surface of Horsfield's treeshrew, and the variations of these papillae are very dependent on the pattern, type of food and the function of the tongue.

Anti-inflammatory activity of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid in LPS-induced rat model.

INTRODUCTION: Salicylic acid derivate is very popular for its activity to suppress pain, fever, and inflammation. One of its derivatives is acetylsalicylic acid (ASA) which has been reported repeatedly that, as a non-steroidal anti-inflammatory drug (NSAID), it has a cardioprotective effect. Although ASA has various advantages, several studies have reported that it may induce severe peptic ulcer disease. We recently synthesized a new compound derived from salicylic acid, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl) which still has the benefit of acetylsalicylic acid as an analgesic and antiplatelet, but lacks its harmful side effects (Caroline et al., 2019). In addition, in silico studies of 3-CH2Cl showed a higher affinity towards protein receptor cyclooxygenase-2 (COX-2; PDB: 5F1A) than ASA. We hypothesized that 3-CH2Cl inhibits the COX-2 activity which could presumably decrease the inflammatory responses. However, no knowledge is available on the anti-inflammatory response and molecular signaling of this new compound. Hence, in this study, we investigated the potential functional relevance of 3-CH2Cl in regulating the inflammatory response in lipopolysaccharide (LPS)-induced rats. The results of this study show that this compound could significantly reduce the inflammatory parameter in LPS-induced rats. MATERIAL AND METHODS: Rats were induced with LPS of 0.5 mg/kg bw intravenously, prior oral administration with vehicle (3% Pulvis Gummi Arabicum / PGA), 500 mg/60 kg body weight (bw; rat dosage converted to human) of 3-CH2Cl and ASA. The inflammatory parameters such as changes in the temperature of septic shock, cardiac blood plasma concentrations of IL-1ß and TNF-α (ELISA), blood inflammation parameters, white blood cell concentrations, and lung histopathology were observed. Meanwhile, the stability of 3-CH2Cl powder was evaluated. RESULT: After the administration of 500 mg/60 kg bw of 3-CH2Cl (rat dosage converted to human) to LPS-induced rats, we observed a significant reduction of both TNF-α (5.70+/-1.04 × 103 pg/mL, p=<0.001) and IL-1ß (2.32+/-0.28 × 103 pg/mL, p=<0.001) cardiac blood plasma concentrations. Besides, we found a reduction of white blood cell concentration and the severity of lung injury in the 3-CH2Cl group compared to the LPS-induced rat group. Additionally, this compound maintained the rat body temperature within normal limits during inflammation, preventing the rats to undergo septic shock, characterized by hypothermic (t = 120 min.) or hyperthermic (t = 360 min) conditions. Furthermore, 3-CH2Cl was found to be stable until 3 years at 25°C with a relative humidity of 75 ± 5%. CONCLUSION: 3-CH2Cl compound inhibited inflammation in the LPS-induced inflammation response model in rats, hypothetically through binding to COX-2, and presumably inhibited LPS-induced NF-κß signaling pathways. This study could be used as a preliminary hint to investigate the target molecular pathways of 3-CH2Cl as a novel and less toxic therapeutical agent in alleviating the COX-related inflammatory diseases, and most importantly to support the planning and development of clinical trial.

In silico molecular docking and in vitro analysis of ethanolic extract Ocimum sanctum Linn.: Inhibitory and apoptotic effects against non-small cell lung cancer.

BACKGROUND AND AIM: Lung cancer, especially non-small cell lung cancer (NSCLC), has been identified as the leading cause of cancer deaths worldwide. The mortality rate from lung cancer has been estimated to be 18.4%. Until now, conventional treatments have not yielded optimal results, thus necessitating an investigation into the use of traditional herbal plants as potential candidates for its treatment. This study aimed to determine the inhibitory and apoptotic activity of the ethanolic extract from Ocimum sanctum Linn. (EEOS) by in silico molecular docking and through in vitro studies using NSCLC cells (A549 cell line). MATERIALS AND METHODS: Dried simplicia of Ocimum sanctum was converted into EEOS using the maceration method. Spectrophotometry was then employed to analyze the EEOS compound. The known main active compounds were further analyzed for inhibitory and apoptotic effects on gene signaling using in silico molecular docking involving the downloading of active compounds from PubChem and target proteins from the Protein Data Bank; the active compounds and proteins were then prepared using the Discovery Studio software v. 19.0.0 and the PyRX 0.8 program, interacted with the HEX 8.0.0 program, and visualized with the Discovery Studio Visualizer v. 19.0. Finally, an in vitro analysis was performed using an antiproliferative-cytotoxic test (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay in the NSCLC A549 cell line). RESULTS: The analysis revealed that the active compounds in the ethanolic extract were dominated by quercetin (flavonoids) (47.23% b/b) and eugenol (phenolic) (12.14% b/b). These active compounds interacted with the active sites (residual amino acids) of the αvß3 integrin, a5b1 integrin, caspase-3, caspase-9, and vascular endothelial growth factor. Hydrogen bonds and Pi-cation and Pi-alkyl interactions were involved in the relationships between the active compounds and the active sites and thus may reveal an antioxidant property of the extract. Furthermore, in vitro analysis showed the inhibitory and antiproliferative effects of the EEOS against non-small cell cancer (A549). CONCLUSION: Taken together, our data showed the ability of EEOS as an inhibitor and apoptotic agent for lung cancer; however, further research is needed to determine the exact mechanism of EEOS as an herbal medication.