Clinacanthus nutans leaf extract reduces pancreatic ß-cell apoptosis by inhibiting JNK activation and modulating oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Background: Controlling apoptosis induced by oxidative stress in pancreatic ß-cells provides promising strategies for preventing and treating diabetes. Clinacanthus nutans leaves possess bioactive constituents with potential antioxidant and anti-diabetic properties. Aim: This study aimed to investigate the molecular mechanisms by which C. nutans extract protects pancreatic ß-cells from apoptotic damage in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitoneal injection of 45 mg/kg STZ, followed by 28 days of treatment with C. nutans leaf extract and Glibenclamide as the standard drug. At the end of the study, blood samples were collected to measure glucose levels, oxidative stress markers, and inflammation. Pancreatic tissue was stained immunohistochemically to detect c-Jun N-terminal kinase (JNK) and Caspase-3 expression. Results: The administration of C. nutans leaf extract to diabetic rats significantly reduced fasting blood glucose, malondialdehyde, and tumor necrosis factor-α levels, while concurrently enhancing the activity of superoxide dismutase. The immunohistochemical studies revealed a decrease in the expression of JNK and caspase-3 in the pancreatic islets of diabetic rats. Conclusion: Clinacanthus nutans exhibits the potential to protect pancreatic ß-cells from apoptosis by suppressing oxidative stress and inflammation.

Prevalence and predictors of discharge polypharmacy in geriatric patients discharged from an Indonesian teaching hospital: a retrospective observational study / Prevalencia y predictores de polifarmacia al alta en pacientes geriátricos dados de alta de un hospital universitario de Indonesia: un estudio observacional retrospectivo

Objective: The study aimed to investigate the prevalence and risk factors for discharge polypharmacy in geriatric patients in Indonesia. Methods: The retrospective cohort study used the medical record profiles of geriatric patients aged ≥ 60 years admitted to the inpatient ward between July 2018 and October 2019. Using three logistic regression models, we assessed the association of the patient’s demographic, clinical characteristics, and disease condition with discharge polypharmacy. The use of five or more medications was defined as discharge polypharmacy. Results: A total of 1533 patients were included in the study. Most patients (78.21%) aged between 60 and 74 years. The male-to-female patient ratio was almost the same (50.16% versus 49.83%). Of the patients (52.51%) were discharged with polypharmacy. According to regression model I, patients who had a chronic condition, comorbidity, stayed in the hospital for ≥ seven days, had a Charlson comorbidity index score (3-4), and received excessive polypharmacy (≥ 10 drugs) during admission had significantly more risk (p< 0.05) to receive polypharmacy at discharge. The results of model II investigated myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, diabetes with complications, renal disease, and high blood pressure as significant (p<0.05) predictors of discharge polypharmacy. The combined model III evaluated that comorbidity, length of hospital stay (7 or more days), excessive polypharmacy use in the hospital, myocardial infarction, and congestive heart failure were significantly (P < 0.05) associated with discharge polypharmacy. Conclusions: Polypharmacy is common in Indonesia and is linked to certain chronic conditions and other clinical factors. A particular plan that includes a pharmacist and physician collaborative relationship and awareness of the health outcomes of polypharmacy could be critical.(AU)

Profiling the Antidiabetic Potential of Compounds Identified from Fractionated Extracts of Entada africana toward Glucokinase Stimulation: Computational Insight.

Glucokinase plays an important role in regulating the blood glucose level and serves as an essential therapeutic target in type 2 diabetes management. Entada africana is a medicinal plant and highly rich source of bioactive ligands with the potency to develop new target drugs for glucokinase such as diabetes and obesity. Therefore, the study explored a computational approach to predict identified compounds from Entada africana following its intermolecular interactions with the allosteric binding site of the enzymes. We retrieved the three-dimensional (3D) crystal structure of glucokinase (PDB ID: 4L3Q) from the online protein data bank and prepared it using the Maestro 13.5, Schrödinger Suite 2022-3. The compounds identified were subjected to ADME, docking analysis, pharmacophore modeling, and molecular simulation. The results show the binding potential of the identified ligands to the amino acid residues, thereby suggesting an interaction of the amino acids with the ligand at the binding site of the glucokinase activator through conventional chemical bonds such as hydrogen bonds and hydrophobic interactions. The compatibility of the molecules was highly observed when compared with the standard ligand, thereby leading to structural and functional changes. Therefore, the bioactive components from Entada africana could be a good driver of glucokinase, thereby paving the way for the discovery of therapeutic drugs for the treatment of diabetes and its related complications.

Emergence of mRNA vaccines in the management of cancer.

INTRODUCTION: mRNA vaccines have been developed as a promising cancer management. It is noted that specification of the antigen sequence of the target antigen is necessary for the design and manufacture of an mRNA vaccine. AREAS COVERED: The steps involved in preparing the mRNA-based cancer vaccines are isolation of the mRNA cancer from the target protein using the nucleic acid RNA-based vaccine, sequence construction to prepare the DNA template, in vitro transcription for protein translation from DNA into mRNA strand, 5' cap addition and poly(A) tailing to stabilize and protect the mRNA from degradation and purification process to remove contaminants produced during preparation. EXPERT OPINION: Lipid nanoparticles, lipid/protamine/mRNA nanoparticles, and cell-penetrating peptides have been used to formulate mRNA vaccine and to ensure vaccine stability and delivery to the target site. Delivery of the vaccine to the target site will trigger adaptive and innate immune responses. Two predominant factors of the development of mRNA-based cancer vaccines are intrinsic influence and external influence. In addition, research relating to the dosage, route of administration, and cancer antigen types have been observed to positively impact the development of mRNA vaccine.

Allergic rhinitis behavioral changes after Indonesian house dust mites allergenic extract administration as immunotherapy.

Background: Allergy is a hypersensitivity reaction that is generally mediated by Immunoglobulin E (IgE). More than 25% of the world's population is suspected of having these various diseases, and the prevalence and progression of these diseases have continued to increase significantly in recent years. Among these allergyrelated diseases, allergic rhinitis and food allergy are the types of allergies with the highest prevalence. Clinical manifestations of allergic rhinitis include sneezing, rhinorrhea, nasal itching, and nasal congestion. Objective: This study aimed to determine the behavioral changes of allergic rhinitis after Indonesian House Dust Mites (IHDM) allergenic extract administration as an immunotherapy. Methods: Eight male BALB/c mice aged 6-8 weeks in each group were treated for seven groups. The sensitization phase is given intraperitoneal, the desensitization phase is given by subcutaneous, and the challenge phase is given intranasal. The allergic parameters were observed, such as nose rubbing and sneezing. The parameters were observed for 15 minutes after the challenge administration. Results: The results showed that the administration of Indonesian House Dust Mites as immunotherapy decreased the frequency of nose rubbing and sneezing after the administration of immunotherapy compared to the allergic rhinitis model. Conclusions: The administration of the Indonesian House Dust Mites as immunotherapy decreased the allergic rhinitis immune response by altering the behavioral parameter.

Development of gastro-food allergy model in shrimp allergen extract-induced sensitized mice promotes mast cell degranulation.

Background: Food allergies have become more common in the last decade. Shrimp is one of the most dominant food allergy triggers in Asian countries, including Indonesia. After ingesting allergens, B cells will produce allergen-specific Immunoglobin E (IgE). In the sensitization period, repeated allergen exposure promotes Mast Cell (MC) degranulation in intestinal tissue and releases several inflammatory mediators, thereby causing hypersensitivity reactions. Shrimp Allergen Extract (SAE) is an immunotherapy and diagnostic agent currently being developed in Indonesia. In this study, we investigated the effect of SAE administration on eliciting an MC immunological response. Methods: Mice were divided into a non-sensitized and sensitized group. The non-sensitized group only received 1 mg of alum (i.p), whereas the sensitized group received 1 mg of alum and 100 µg of SAE on days 0, 7, and 14. Then, both groups were challenged with 400 µg SAE (p.o) on days 21, 22, and 23 following systemic allergic symptom observation. Results: We showed that SAE was able to increase systemic allergic symptoms significantly in the sensitized mice through repeated challenge (1.33±0.21; 1.83±0.17; and 2.00±0.00), compared to non-sensitized mice (0.17±0.17). Moreover, histopathological analysis showed that the SAE administration causes an increase of MC degranulation in the ileum tissue of the sensitized mice (44.43%±0.01), compared to non-sensitized mice (35.45%±0.01). Conclusions: This study found that SAE could induce allergic reactions in mice by influencing critical effector cells, MCs.

Prevalence and Predictors of Excessive Polypharmacy in Geriatric Inpatients: A Retrospective Cross-Sectional Study in Indonesia.

OBJECTIVES: To investigate the prevalence and predictors of excessive polypharmacy in geriatric inpatients in Indonesia. METHODS: This retrospective cross-sectional study included 1533 inpatients over the age of 60 years at Universitas Airlangga Hospital, Indonesia. Effects of a patient's baseline characteristics on excessive polypharmacy were evaluated using logistic regression analysis. RESULTS: Excessive polypharmacy was observed in 133 (8.67%) patients. Ulcer (OR 8.151,95% CI 2.234-29.747, P = .001), cancer (OR 5.551, 95% CI 1.602-19.237, P = .007), and renal diseases (OR 3.710, 95% CI 1.965-7.006, P < .001) were the 3 strongest predictors of excessive polypharmacy. An association between hospital stay of more than 3 days and excessive polypharmacy was identified (OR 2.382, 95% CI 1.109-5.115, P = .026). DISCUSSION: One in 12 elderly Indonesians was found to practice excessive polypharmacy. Several chronic conditions and increased length of hospital stay were the factors associated with excessive polypharmacy.

Epigallocatechin Gallate Ameliorates Nicotine Withdrawal Conditions-Induced Somatic and Affective Behavior Changes in Mice and Its Molecular Mechanism.

In nicotine withdrawal (NW) conditions, molecular changes, such as increasing corticotropin-releasing factor (CRF) in the amygdala, and melanocortin signaling in the hypothalamus, can occur in the brain, leading to increased feeding behavior and body weight as somatic changes as well as high anxiety-like behavior as an affective changes. Therefore, this research aimed to investigate the effect of epigallocatechin gallate (EGCG), the largest component in green tea, on CRF, pro-opiomelanocortin (POMC), and melanocortin four receptor gene expression in the brain under NW conditions. The 24 Balb/c male mice used were randomly divided into four groups. The doses used included normal saline 1.0 mL/kg as a control group, and nicotine 3.35 mg/kg that was administered subcutaneously three times a day. After NW conditions, EGCG 50 mg/kg was administered intraperitoneally two times a day. Behavior evaluation was performed to measure somatic and affective changes, and the animal was sacrificed for molecular analysis. The results showed that NW conditions significantly increased food intake, body weight, and anxiety-like behavior compared with the normal group. Meanwhile, EGCG significantly decreased food intake, body weight, and anxiety-like behavior compared with NW conditions in mice without EGCG. The polymerase chain reaction results also showed that EGCG decreased the CRF mRNA expression in the amygdala and increased the POMC. This indicated that EGCG improved somatic and affective behavior in NW conditions by decreasing CRF mRNA expression in the amygdala and increasing POMC mRNA expression in the hypothalamus.

The administration of bovine hydroxyapatite-alendronate implant accelerates bone defect healing in an osteoporotic rat.

BACKGROUND: Bone fracture is the main consequence of osteoporosis, which may become a neglected disease. OBJECTIVE: This study aims to fabricate bovine hydroxyapatite-gelatine (BHA-GEL) based bone-implant with alendronate (ALE) in vivo. METHODS: Wistar rats were used for an osteoporotic animal model induced by ovariectomy. There were three groups: negative control, BHA-GEL implant, and BHA-GEL-ALE implant. Each group performed a defect by drilling the femur (diameter of 2.2 mm and depth of 2 mm). Observations on the closure of bone defects were performed by X-ray radiography at the second and sixth week after surgery. The mechanism of bone healing was observed by using hematoxylin-eosin (HE) staining and immunohistochemical technique with anti-vascular endothelial growth factor (VEGF) and anti-alkaline phosphatase (ALP) antibodies. RESULTS: The radiograph examination showed the implanted group had accelerated bone growth. In addition, the osteoblast, osteoclast and osteocyte had accelerated migration to the defect area. Moreover, the immunoreactive score (IRS) of VEGF at the sixth week in the BHA-GEL-ALE group was lower than the other groups. Meanwhile, the IRS of ALP in BHA-GEL-ALE was higher compared to other groups. CONCLUSION: The BHA-GEL-ALE implant accelerates the healing of bone defect in the osteoporotic rat by increasing the ALP expression and the total number of cells.

PEGylated liposomes enhance the effect of cytotoxic drug: A review.

Cancer is a second leading disease-causing death worldwide that will continuously grow as much as 70% in the next 20 years. Chemotherapy is still becoming a choice for cancer treatment despite its severity of side effects and low success rate due to ineffective delivery of the chemodrugs. Since it was introduced in 1960, significant progress has been achieved in the use of liposomes in drug delivery. The study aims to review relevant literatures on role of PEGylated liposome in enhancing cytotoxic activity of several agents. A systematic literature on the use of PEGylated liposomes in anticancer research via Scopus, Google scholar and PubMed databases was conducted for studies published from 2000 to 2022. A total of 15 articles were selected and reviewed from 312 articles identified covering a variety of anticancer treatments by using PEGylated liposomes. PEGylated liposome which is purposed to achieve steric equilibrium is one of enhanced strategies to deliver anticancer drugs. It has been shown that some improvement of delivery and protection form a harsh gastric environment of several anticancer drugs when they are formulated in a PEGylated liposome. One of the successful drugs that has been clinically used is Doxil®, followed by some other drugs in the pipeline Various drugs (compounds) had been used to enhance the efficacy of PEGylated liposomes for targeted cancer cells in vitro and in vivo. In conclusion, PEGylated liposomes enhance drug activities and have great potential to become efficient anticancer delivery to follow Doxil® in the clinical setting.

Computational approach in searching for dual action multitarget inhibitors for osteosarcoma.

Osteosarcoma is a common primary malignant bone tumor that typically manifests in the second decade of life. This study aimed to identify osteogenic compounds that potentially serve as multitarget inhibitors for osteosarcoma. The study was a molecular docking study of nine Food and Drug Administration-approved compounds with osteogenic properties to the key membrane proteins of osteosarcoma. The ligands used were raloxifene, simvastatin, dexamethasone, risedronate, ibandronate, zoledronic acid, ascorbic acid, alendronate, and ß-glycerophosphate, whereas the target proteins used were RET, fibroblast growth factor receptor 1, KIT, PDGFRA, VEGFR1, and VEGFR2. Chem3D version 15.0.0.106 was used for ligand preparation, and AutoDockTools version 1.5.6 was used for protein preparation, whereas molecular docking was conducted using AutoDock Vina. Raloxifene, simvastatin, and dexamethasone had the lowest binding activity to the target proteins. The binding affinity of raloxifene was from -8.4 to -10.0 kcal mol-1, that of simvastatin was -8.3 to -9.2 kcal mol-1, whereas dexamethasone ranged from -6.9 to -9.1 kcal mol-1. Most types of interactions were hydrophobically followed by hydrogen bonding. The current study suggests that raloxifene, simvastatin, and dexamethasone have the potential to act as multitarget inhibitors for osteosarcoma with the ability to induce bone remodeling.

Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor.

The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.

Bovine hydroxyapatite-based scaffold accelerated the inflammatory phase and bone growth in rats with bone defect.

Hydroxyapatite (HA) is a biomaterial widely used to treat bone defect, such as due to traffic accident. The HA scaffold is obtained from synthetic HA or natural sources, such as bovine hydroxyapatite (BHA). This study aims to compare the characteristics and in vivo performance of BHA-based and HA-based scaffolds. For this purpose, the scaffold was formulated with gelatin (GEL) and characterised by SEM-EDX, FTIR and mini autograph. The defect model was carried out on the femur area of Wistar rats classified into three animal groups: defect, HA-GEL and BHA-GEL. Postoperatively (7, 14 and 28 days), the bone was radiologically evaluated, and stained with haematoxylin-eosin, anti-CD80 and anti-CD163. The BHA-GEL scaffold showed a regular surface and spherical particle shape, whereas the HA-GEL scaffold exhibited irregular surface. The BHA-GEL scaffold had higher pore size and compressive strength and lower calcium-to-phosphorus ratio than the HA-GEL scaffold. In vivo study showed that the expression of CD80 in the three experimental groups was not significantly different. However, the expression of CD163 differed significantly between the groups. The BHA-GEL group showed robust expression of CD163 on day 7, which rapidly decreased over time. It also showed increased osteoclasts, osteoblasts and osteocytes cell count that contributed to the integrity of the defect area. In conclusion, the BHA-based scaffold exhibited the desired physical and chemical characteristics that benefit in vivo performance versus the HA-based scaffold. Thus, the BHA-based scaffold may be used as a bone graft.

Differentiation of osteoblasts: the links between essential transcription factors.

Osteoblasts, cells derived from mesenchymal stem cells (MSCs) in the bone marrow, are cells responsible for bone formation and remodeling. The differentiation of osteoblasts from MSCs is triggered by the expression of specific genes, which are subsequently controlled by pro-osteogenic pathways. Mature osteoblasts then differentiate into osteocytes and are embedded in the bone matrix. Dysregulation of osteoblast function can cause inadequate bone formation, which leads to the development of bone disease. Various key molecules are involved in the regulation of osteoblastogenesis, which are transcription factors. Previous studies have heavily examined the role of factors that control gene expression during osteoblastogenesis, both in vitro and in vivo. However, the systematic relationship of these transcription factors remains unknown. The involvement of ncRNAs in this mechanism, particularly miRNAs, lncRNAs, and circRNAs, has been shown to influence transcriptional factor activity in the regulation of osteoblast differentiation. Here, we discuss nine essential transcription factors involved in osteoblast differentiation, including Runx2, Osx, Dlx5, ß-catenin, ATF4, Ihh, Satb2, and Shn3. In addition, we summarize the role of ncRNAs and their relationship to these essential transcription factors in order to improve our understanding of the transcriptional regulation of osteoblast differentiation. Adequate exploration and understanding of the molecular mechanisms of osteoblastogenesis can be a critical strategy in the development of therapies for bone-related diseases.Communicated by Ramaswamy H. Sarma.

In vivo study of bovine hydroxyapatite-gelatin-hydroxypropyl methylcellulose with alendronate as injectable bone substitute composite in osteoporotic animal model.

The injectable bone substitute (IBS) is a self-setting local drug delivery system that adjusts the shape of the bone gap in the fracture. This study aimed to examine the effectiveness of IBS composites of bovine hydroxyapatite (BHA) and alendronate (Ale) in accelerating bone growth in osteoporotic rats. IBS was made by mixing BHA with gelatin 5%, hydroxypropyl methylcellulose (HPMC) 2%, and Ale 10%. The physical properties of IBS were viscosity, injectability, and density tests. Twenty-four female Wistar rats were divided into four groups. After 8 weeks, 2 mm gap was made in the right femur of all rats and filled with IBS. The healing process was observed after 6 weeks with X-ray imaging and H and E staining. The obtained results showed viscosity, injectability, and density value of IBS from 30.4 to 39.4 dPa.s, 98.22%-98.64%, and 0.6325-0.8409 g/cm3, respectively. X-ray imaging and histology results proved the condition of osteoporosis in rats with ovariectomy. The addition of BHA-Gel-HPMC-Ale significantly affected the number of osteoblasts, osteocytes, and osteoclasts (P < 0.05). After 45 days of observation, the addition of BHA-Gel-HPMC-Ale showed the highest mean number of osteoblasts, osteocytes, and osteoclasts, which were 25.00 ± 3.00, 64.33 ± 11.15, and 5.67 ± 0.58 compared to BHA-Gel-HPMC and positive control groups. The BHA-Gel-HPMC-Ale IBS has the potential to reverse osteoporosis. Nevertheless, the underlying potential of these biomaterials to reverse osteoporosis needs further research.

Acceleration of Bone Fracture Healing through the Use of Bovine Hydroxyapatite or Calcium Lactate Oral and Implant Bovine Hydroxyapatite-Gelatin on Bone Defect Animal Model.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA-GEL (bovine hydroxyapatite-gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA-GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA-GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA-GEL pellet implants.

Effectiveness of Indonesian house dust mite allergenic extract in triggering allergic rhinitis sensitivity in a mouse model: A preliminary study.

Background and Aim: Perennial allergic rhinitis (AR) is a chronic upper respiratory disease, with inflammation mediated by immunoglobulin E in the nasal mucosa caused by house dust mites. Recently, allergen immunotherapy showed promising allergic healing in patients with a definite history of sensitization. Based on this finding, a product was developed using Indonesian house dust mite (IHDM). This study aimed to optimize the allergenic rhinitis mouse model that was generated using IHDM to test the in vivo sensitivity and safety of this product. Materials and Methods: Seven groups of mice were used for effectiveness testing - normal, negative control with IHDM challenge, positive control with 0.1% histamine challenge, and AR group by both IHDM-induced sensitization at 12.5, 50, 250, or 500 µg and IHDM challenge. Mice were sensitized by intraperitoneal administration of IHDM once a week for 3 consecutive weeks. Thereafter, the challenge was given intranasally 5 times on alternate days. The number of nose rubbing and sneezing was noted. Eosinophil infiltration was assessed histologically using hematoxylin and eosin staining. The expression of interleukin-5 (IL-5) mRNA in the nasal mucosa was determined using semi-quantitative reverse transcription-polymerase chain reaction. Results: The induction of AR with IHDM significantly increased the number of nose rubbing and sneezing in the mouse model. Eosinophil infiltration was observed in the nasal mucosa; however, no significant change occurred in the expression of IL-5 mRNA. Conclusion: Overall, these data indicate that IHDM allergenic extract could be an effective sensitizing agent in a mouse model of AR. Although the use of IHDM is a limitation of this study because other sources of house dust mites might have different effects, this study provides a proper model for immunotherapy effectivity testing for in vivo pre-clinical studies.

Optimisation of Vitamin B12 Extraction from Green Edible Seaweed (Ulva lactuca) by Applying the Central Composite Design.

Vitamin B12, only found naturally in animal-based foods, is essential for brain functions and various chemical reactions in the human body. Insufficient vitamin B12 leads to vitamin B12 deficiency, common among strict vegetarians due to their limited intake of animal-based foods. Nevertheless, extensive studies have demonstrated that macroalgae, specifically the Ulva lactuca species, are rich in vitamin B12 and could be further exploited in future dietary applications. In the current study, the ideal extraction method of vitamin B12 from dried U. lactuca was developed and optimised to achieve the maximum vitamin B12 yield. The effects of several extraction parameters, including the solvent-to-solvent, methanol:water (MeOH:H2O), and solute-to-solvent ratios, and pH on the total vitamin B12 content were analysed through a two-level factorial and central composite design. The highest vitamin B12 content, particularly cyanocobalamin (CN-Cbl), was recovered through the ultrasonic-assisted extraction (UAE) of oven-dried U. lactuca at 3 g:60 mL of solute-to-solvent and 25:75% of MeOH to H2O ratios at pH 4. The extraction of CN-Cbl from oven-dried U. lactuca that employed the UAE method has elevated CN-Cbl content recovery compared to other extraction methods.

Traditional Uses, Phytochemistry and Biological Activities of Alocasia Species: A Systematic Review.

The genus Alocasia (Schott) G. Don consists of 113 species distributed across Asia, Southeast Asia, and Australia. Alocasia plants grow in tropical and subtropical forests with humid lowlands. Featuring their large green heart-shaped or arrow-shaped ear leaves and occasionally red-orange fruit, they are very popular ornamental plants and are widely used as traditional medicines to treat various diseases such as jaundice, snake bite, boils, and diabetes. This manuscript critically analysed the distribution, traditional uses, and phytochemical contents of 96 species of Alocasia. The numerous biological activities of Alocasia species were also presented, which include anti-cancer, antidiabetic and antihyperglycaemic, antioxidant, antidiarrhoea, antimicrobial and antifungal, antiparasitic (antiprotozoal and anthelminthic), antinociceptive and anti-inflammatory, brine shrimp lethality, hepatoprotective, anti-hemagglutinin, anti-constipation and diuretic, and radioprotective activities as well as acute toxicity studies. Research articles were acquired by the accessing three scientific databases comprising PubMed, Scopus, and Google Scholar. For this review, specific information was obtained using the general search term "Alocasia", followed by the "plant species names" and "phytochemical" or "bioactivity" or "pharmacological activity". The accepted authority of the plant species was referred from theplantlist.org. Scientific studies have revealed that the genus is mainly scattered throughout Asia. It has broad traditional benefits, which have been associated with various biological properties such as cytotoxic, antihyperglycaemic, antimicrobial, and anti-inflammatory. Alocasia species exhibit diverse biological activities that are very useful for medical treatment. The genus Alocasia was reported to be able to produce a strong and high-quality anti-cancer compound, namely alocasgenoside B, although information on this compound is currently limited. Therefore, it is strongly recommended to further explore the relevant use of natural compounds present in the genus Alocasia, particularly as an anti-cancer agent. With only a few Alocasia species that have been scientifically studied so far, more attention and effort is required to establish the link between traditional uses, active compounds, and pharmacological activities of various species of this genus.

Natural Products-Based Metallic Nanoparticles as Antimicrobial Agents.

Natural products offer a wide range of bioactivity including antimicrobial properties. There are many reports showing the antimicrobial activities of phytochem icals from plants. However, the bioactivity is limited due to multidrug resistant properties of the microorganism and different composition of cell membrane. The antibacterial activity of the natural products is different toward Gram-negative and Gram-positive bacteria. These phenomena are caused by improper physicochemical conditions of the substance which hinder the phytochemical bioactivity against the broad range of bacteria. One of the strategies to improve the antimicrobial action is by biogenic synthesis via redox balance of the antimicrobial active substance with metal to form nanosized materials or nanoparticles (NPs). Antibiotic resistance is not relevant to NPs because the action of NPs is via direct contact with bacterial cell walls without the need of penetration into microbial cells. The NPs that have shown their effectiveness in preventing or overcoming biofilm formation such as silver-based nanoparticles (AgNPs), gold-based nanoparticles (AuNPs), platinum-based nanoparticles (PtNPs) and Zinc oxide-based nanoparticles (ZnONPs). Due to its considerably simple synthesis procedure has encouraged researchers to explore antimicrobial potency of metallic nanoparticles. Those metallic nanoparticles remarkably express synergistic effects against the microorganisms tested by affecting bacterial redox balance, thus disrupting their homeostasis. In this paper, we discuss the type of metallic nanoparticle which have been used to improve the antimicrobial activity of plant extract/constituents, preparation or synthesis process and characterisation of the plant-based metallic nanoparticles.