Tryptophan and Its Derived Metabolites as Biomarkers for Tuberculosis Disease: A Systematic Review

Feasible diagnostic assays are required to detect new tuberculosis (TB) cases and monitor treatment. This study aimed to evaluate evidence on tryptophan (Trp) and its metabolites as proposed biomarkers for TB. Through specific keyword searches, we identified 170 relevant literature sources and included seven publications (from 2013 to 2023). The biomarker used in these studies were indoleamine 2, 3-dioxygenase (IDO) activity, IDO-1 gene expression, and plasma IDO protein, measured using ELISA, liquid chromatography-mass spectrometry, ultraperformance liquid chromatography mass spectrometry, and transcriptional profiling. The studies encompassed a pediatric case-control and six studies involving adults, pregnant women with TB-HIV, and individuals with multidrug-resistant tuberculosis, active TB, and latent TB. The assessment of IDO activity and IDO protein level demonstrated promising performance in distinguishing active TB from controls and in evaluating treatment failure and recurrent cases to controls. Trp and its metabolites fulfilled nearly all of target product profile criteria for detecting active TB. This study highlights the potential of utilizing host Trp and its metabolites as non-sputum-based biomarker for TB infection.

Rifampicin Resistant Tuberculosis Among Presumptive Pulmonary Tuberculosis in Province Referral Hospital, Indonesia: Dynamic Cases of a 7-Year Report.

BACKGROUND: Indonesia has the second highest tuberculosis (TB) cases globally. This study aimed to determine the sociodemographic factors associated with TB and rifampicin-resistant tuberculosis (RR-TB) cases among presumptive pulmonary TB patients in Aceh Referral Hospital. Study Design: A retrospective cross-sectional study. METHODS: A retrospective cross-sectional review of presumptive pulmonary TB patients having a sputum test at the clinical microbiology laboratory was conducted from January 2015 to December 2021. Patient characteristics and drug susceptibility data were abstracted from the hospital information system of TB (SITB) and analyzed by univariate and bivariate analysis. RESULTS: The Mycobacterium tuberculosis (MTB) was detected in 32.8% sample (1,521/4,637). Of the TB-confirmed cases, 14.1% (215/1,521) were resistant to rifampicin (RR-TB). Most of them were male patients (71.63%), were in the age range of 35-54 years (48.7%), lived in rural areas of the country (56.3%), and were previously TB-treated cases (65.5%). Overall, 35-44-year-old patients (adjusted odds ratio [AOR]=2.11, 95% CI=1.25, 3.5, P<0.05) were more likely to have RR-TB compared to>65-year-old patients. Gender and residence were not associated with RR-TB (P>0.05). Case detection decreased in pandemic conditions (19.5% in 2019 to 13.9% and 7.91% in 2020 and 2021, respectively). CONCLUSION: The findings revealed the dynamic cases and sociodemographic factors of TB and RR-TB in a province referral hospital in Indonesia for 7 years. The cases of TB and RR-TB among presumptive TB patients were 32.8% and 14.1%, respectively. The cases were found to be more noticeable in males, adults (45-54 years old), and patients residing in rural areas.

Knowledge and acceptance associated with medication adherence among hypertension individuals in Aceh province, Indonesia.

Low adherence to anti-hypertensive medication is observed among individuals in Aceh, the westernmost province of Indonesia. Since uncontrolled hypertension has the potential to develop into a life-threatening disease, exploring medication adherence among this specific population is essential. Therefore, this study aimed to evaluate knowledge and acceptance associated with medication adherence among hypertensive individuals in Aceh Province. A cross-sectional study was conducted from March to July 2023 on 534 respondents diagnosed with hypertension, who were selected using the random sampling method. Demographic characteristics collected included body height and weight, age, gender, education, ethnicity, and occupation. Acceptance and knowledge were measured through a set of standardized questionnaires while the Morisky Medication Adherence Scale-8 was used for evaluating medication adherence. Logistic regression with a multinomial model was used to assess the correlations of acceptance and knowledge with medication adherence. The results showed that only 28.5 % of the respondents had high adherence to anti-hypertensive medication. Furthermore, a high level of acceptance towards hypertension significantly predicted medication adherence (p < 0.001; OR = 9.14 [95%CI: 3.49-23.94]). Knowledge about dosing frequency, the benefits of low-fat and sodium diets, and the negative impacts of drinking alcohol were correlated with high-level adherence (p < 0.01). Meanwhile, knowledge about renal complications correlated negatively with adherence level (p = 0.002; OR = 0.32 [95%CI: 0.16-0.66]). In conclusion, this study showed that acceptance and knowledge of hypertension correlated with the level of medication adherence.

The Effects of Lumbricus rubellus Extract on Staphylococcus aureus Colonization and IL-31 Levels in Children with Atopic Dermatitis.

Background and Objectives: The ineffective combination of corticosteroids and antibiotics in treating some atopic dermatitis (AD) cases has been concerning. The skin barrier defects in AD ease the colonization of Staphylococcus aureus (S. aureus), which results in a rise in interleukin-31 (IL-31). Lumbricus rubellus (L. rubellus) has shown antimicrobial and antiallergic effects but has not been studied yet to decrease the growth of S. aureus and IL-31 levels in AD patients. This study aimed to analyze the effect of L. rubellus extract in reducing S. aureus colonization, the IL-31 level, and the severity of AD. Materials and Methods: A randomized controlled trial (RCT) (international registration number TCTR20231025004) was conducted on 40 AD patients attending Dermatology and Venereology Polyclinic, Mother and Child Hospital (RSIA), Aceh, Indonesia, from October 2021 to March 2022. AD patients aged 8-16 who had a Scoring Atopic Dermatitis (SCORAD) index > 25, with total IgE serum level > 100 IU/mL, and had healthy weight were randomly assigned into two groups: one received fluocinolone acetonide 0.025% and placebo (control group) and one received fluocinolone acetonide 0.025% combined with L. rubellus extract (Vermint®) (intervention group). The S. aureus colony was identified using a catalase test, coagulase test, and MSA media. The serum IL-31 levels were measured using ELISA assay, while the SCORAD index was used to assess the severity of and improvement in AD. Mean scores for measured variables were compared between the two groups using an unpaired t-test and Mann-Whitney U test. Results: A significant decline in S. aureus colonization (p = 0.001) and IL-31 (p = 0.013) in patients receiving L. rubellus extract was found in this study. Moreover, fourteen AD patients in the intervention group showed an improvement in the SCORAD index of more than 35% (p = 0.057). Conclusions: L. rubellus extract significantly decreases S. aureus colonization and the IL-31 level in AD patients, suggesting its potential as an adjuvant therapy for children with AD.

Antioxidant and phytometabolite profiles of ethanolic extract from the cascara pulp of Coffea arabica collected from Gayo Highland: A study for potential anti-photoaging agent.

Background: As the most abundant coffee by-product, cascara pulp has been considered a good source of antioxidants which could be used to prevent photoaging. The aim of this study was to determine the phytometabolite profiles, antioxidant and photoaging properties of the ethanolic extract of Coffea arabica cascara pulp. Methods: Ethanolic maceration was performed on the fine powder of C. arabica cascara pulp collected from Gayo Highland, Aceh Province, Indonesia. The filtrate obtained was evaluated for its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, total phenolic content (TPC), and total flavonoid content (TFC). The phytometabolite profiling was conducted qualitatively using reagents and quantitatively using gas chromatography-mass spectroscopy (GC-MS). The potential of the cascara pulp phytometabolites in inhibiting activator protein-1 (AP-1) was evaluated through molecular docking. Results: The extract had TPC and TFC of 2.04 mg gallic acid equivalent/g extract and 91.81 mg quercetin equivalent/g extract, respectively. The half-maximal inhibitory concentration (IC 50) for the DPPH inhibition reached as low as 9.59 mg/L. Qualitative phytocompound screening revealed the presence of alkaloids, saponins, tannins, flavonoids, steroids, quinones, polyphenols, and triterpenoids. GC-MS revealed the extract containing 5-hydroxy-methylfurfural (22.31%); 2,5-dimethyl-4-hydroxy-3(2H)-furanone (0.74%); and caffeine (21.07%), which could form interaction with AP-1 with binding energies of -172.8, -150.8, and -63.188 kJ/mol, respectively. Conclusion: Ethanolic extract from C. arabica cascara pulp potentially have anti-photoaging properties which is worthy for further investigations in the future.

Antioxidant and antiproliferative activities of n-hexane extract and its fractions from Blumea balsamifera L. leaves.

Blumea balsamifera is a plant species that has been popularly used to treat a broad spectrum of diseases. In efforts of tackling the increasing threat of cancers, B. balsamifera has been studied for its anticancer potentials. Hence, through this research, we aimed to evaluate the antioxidant and antiproliferative activities of n-hexane extract from B. balsamifera L. leaves along with its fractionation products. After the n-hexane extract has been obtained, the sample was column chromatographed using gradient elution with n-hexane:ethyl acetate solvent. All the isolation protocols produced 1 n-hexane extract and 10 different fractions (fractions 1-10). Antioxidant and antiproliferative effects of the samples were assessed based on 2,2-diphenyl-1-picrylhydrazyl and brine shrimp lethality test assay, respectively. None of the samples have a strong antioxidant level because all samples yielded IC50 of more than 100 ppm - the best of them was fraction 8 with IC50 = 113.716 ppm. On contrary, most of the samples were observed to have a potent antiproliferative effect, especially fraction 8 with LC50 = 2.00 ppm. Taken altogether, fraction 8 from the n-hexane extract of B. balsamifera L. leaves is the most potential candidate for proliferative disease therapy, where further studies confirming the results are required.

Coffee by-products as the source of antioxidants: a systematic review.

Background: Solid waste from coffee depulping process threatens the organism in environment as it produces organic pollutants. Evidence suggested that coffee by-product could valorize owing to its potential as antioxidant sources. The aim of this systematic review was to evaluate antioxidant activity of coffee by-products obtained from different coffee variants (arabica and robusta) and processing methods. Methods: The systematic review was conducted as of May 29, 2021 for records published within the last ten years (2011-2021) using seven databases: Embase, Medline, BMJ, Web of Science, Science Direct, Cochrane, and PubMed. Data on type of specimen, processing methods, and antioxidant activities were collected based on PRISMA guidelines. Results: Our data suggested that aqueous extract was found to be the most common processing method used to obtain the antioxidant from various coffee by-products, followed by methanol and ethanol extract. A variety of antioxidant properties ranging from strong to low activity was found depending on the variety, type of coffee by-products (cascara, pulp, husk, silverskin, and parchment), and processing technique. Fermentation employing proper bacteria was found effective in improving the yield of bioactive compounds resulting in higher antioxidant capacity. Applications in feedstuffs, foods, beverages, and topical formulation are among the potential utilization of coffee by-products. Conclusion: Coffee by-products contain bioactive compounds possessing antioxidant properties which could be used as additives in foods, beverages, and cosmetics. In particular, their benefits in skin care products require further investigation.

Antidepressant-like Activity of Patchouli Oil var. Tapak Tuan (Pogostemon cablin Benth) via Elevated Dopamine Level: A Study Using Rat Model.

Essential oils are gaining popularity for their use in treating depression, including that extracted from patchouli leaves and stems (Pogostemon cablin). Herein, we used patchouli oil (PO) containing a high amount of patchouli alcohol derived from P. cablin var. Tapak Tuan. The aim of this study was to investigate the antidepressant potential of PO, with a variety of patchouli alcohol concentrations obtained from a separation process using vacuum distillation with different temperature ranges. The initial patchouli oil (iPO) was traditionally distilled by a local farmer and further distilled using a rotary evaporator at temperature ranges of 115−160 °C (POF-1); 120−160 °C (POF-2), and 125−160 °C (POF-3), resulting in products with different patchouli alcohol concentrations. POF-3, with the highest patchouli alcohol content of 60.66% (based on gas chromatography-mass spectrometry), was used for cooling crystallization, resulting in 100% patchouli alcohol crystal (pPA). A tail suspension test (TST) was performed on a rat model to screen the antidepressant potential of iPO and its derivatives. The TST results revealed that POF-3 had the best antidepressant-like effect and was second only to the fluoxetine-based antidepressant, Kalxetin®, where both groups had significant reductions of immobility time post-treatment (p < 0.0001). Other than patchouli alcohol, POF-3 also contained ledol and trans-geraniol, which have been reported for their antidepressant-related activities. Brain dopamine levels increased significantly in the group treated with POF-3 (p < 0.05 as compared with the control group), suggesting its primary anti-depressant mechanism. These findings suggest the potential of vacuum-distilled patchouli oil in reducing depression via dopamine elevation.

Molecular docking investigation of calotropone as a potential natural therapeutic agent against pancreatic cancer.

A natural bioactive compound named calotropone has been reported as a drug candidate for several cancers, including pancreatic cancers. Herein, we used molecular docking approach to test the possible mechanisms of action of calotropone in inhibiting the growth of pancreatic cell cancer with gemcitabine as the positive control. By employing AutoDock Vina, we studied the molecular interaction between calotropone and pancreatic cancer-associated proteins, namely Glucosaminyl (N-Acetyl) Transferase 3, Glutamic-Oxaloacetic Transaminase 1, Tyrosine-protein kinase Met (c-Met), peroxisome proliferator-activated receptor γ, Budding Uninhibited by Benzimidazole 1, A Disintegrin and Metalloproteinase 10, Sex-determining region Y and Nuclear Factor kappa Beta (Nf-Kß). Higher affinity energies of calotropone toward the aforementioned proteins (ranging from ‒7.3 to ‒9.3 kcal/mol) indicate that calotropone may work in the same manner as anticancer drug gemcitabine. Highest docking score was found at the interaction of calotropone and Nf-Kß (‒9.3 kcal/mol).

Molecular docking of two cytotoxic compounds from Calotropis gigantea leaves against therapeutic molecular target of pancreatic cancer.

The utilization of natural compounds as therapeutic agents to treat pancreatic cancer has recently focused on natural drug research. Calotropis gigantea has long been believed to be a medicinal plant that helps in treating various diseases. The bioactive compounds 9-metoxipinoresinol and isoliquiritigenin isolated from C. gigantea leaves are proven to act as therapeutic agents by inhibiting the cancer cell growth of Panc-1 cells. This study aimed to screen the potential molecular inhibition mechanisms of 9-metoxipinoresinol and isoliquiritigenin against pancreatic cancer development in-silico. We analyzed the activity of the aforementioned two compounds as inhibitors of several proteins that play a role in the growth of pancreatic cancer cells, such as GCNT3, GOT1, c-Met, PPARγ, BUB1, and NF-κß, through molecular docking investigation. Our data suggested that 9-metoxipinoresinol and isoliquiritigenin were able to have well interaction with the target proteins, in which the predicted affinity energy ranged between -6.8 and 8.7 kcal/mol. The docking scores of 9-metoxipinoresinol and isoliquiritigenin were higher than the standard drug used (gemcitabine). Based on the binding affinity energy, GCNT3 and BUB1 are potentially to be used as target molecules for cancer therapy using 9-metoxipinoresinol and isoliquiritigenin, respectively.