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This review identifies terpenes isolated from the medicinal Angiosperms of Asia and the Pacific with antibacterial and/or antifungal activities and analyses their distribution, molecular mass, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and library searches from 1968 to 2022. About 300 antibacterial and/or antifungal terpenes were identified during this period. Terpenes with a MIC ≤ 2 µg/mL are mostly amphiphilic and active against Gram-positive bacteria, with a molecular mass ranging from about 150 to 550 g/mol, and a polar surface area around 20 Ų. Carvacrol, celastrol, cuminol, dysoxyhainic acid I, ent-1ß,14ß-diacetoxy-7α-hydroxykaur-16-en-15-one, ergosterol-5,8-endoperoxide, geranylgeraniol, gossypol, 16α-hydroxy-cleroda-3,13 (14)Z-diene-15,16-olide, 7-hydroxycadalene, 17-hydroxyjolkinolide B, (20R)-3ß-hydroxy-24,25,26,27-tetranor-5α cycloartan-23,21-olide, mansonone F, (+)-6,6'-methoxygossypol, polygodial, pristimerin, terpinen-4-ol, and α-terpineol are chemical frameworks that could be candidates for the further development of lead antibacterial or antifungal drugs.
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Antifúngicos , Magnoliopsida , Antibacterianos/farmacología , Antifúngicos/farmacología , Asia , Terpenos/farmacologíaRESUMEN
Microbes such as the White Spot Syndrome Virus account for severe losses in the shrimp farming industry globally. This review examines the literature on the mangrove plants of Asia and the Pacific with antibacterial, antifungal, or antiviral activities. All of the available data published on this subject were collected from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1968 to 2022. Out of about 286 plant species, 119 exhibited antimicrobial effects, and a total of 114 antimicrobial natural products have been identified including 12 with MIC values below 1 µg/mL. Most of these plants are medicinal. The mangrove plants of Asia and the Pacific yield secondary metabolites with the potential to mitigate infectious diseases in shrimp aquaculture.
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Antifúngicos , Productos Biológicos , Animales , Acuicultura , Antibacterianos/farmacología , Plantas , Crustáceos , Antivirales/farmacologíaRESUMEN
Silver Phosphate, Ag3PO4, being a highly capable clinical molecule, an ultrasonic method was employed to synthesize the M-Ag3PO4, (M = Se, Ag, Ta) nanoparticles which were evaluated for antibacterial and cytotoxicity activities post-characterization. Escherichia coli and Staphylococcus aureus were used for antibacterial testing and the effects of sonication on bacterial growth with sub-MIC values of M-Ag3PO4 nanoparticles were examined. The effect of M-Ag3PO4 nanoparticles on human colorectal carcinoma cells (HCT-116) and human cervical carcinoma cells (HeLa cells) was examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and DAPI (4',6-diamidino-2-phenylindole) staining. Additionally, we analyzed the effect of nanoparticles on normal and non-cancerous human embryonic kidney cells (HEK-293). Ag-Ag3PO4 exhibited enhanced antibacterial activity followed by Ta-Ag3PO4, Ag3PO4, and Se-Ag3PO4 nanoparticles against E. coli. Whereas the order of antibacterial activity against Staphylococcus aureus was Ag3PO4 > Ag-Ag3PO4 > Ta-Ag3PO4 > Se-Ag3PO4, respectively. Percentage inhibition of E. coli was 98.27, 74.38, 100, and 94.2%, while percentage inhibition of S. aureus was 25.53, 80.28, 99.36, and 20.22% after treatment with Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4, respectively. The MTT assay shows a significant decline in the cell viability after treating with M-Ag3PO4 nanoparticles. The IC50 values for Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4 on HCT-116 were 39.44, 28.33, 60.24, 58.34 µg/mL; whereas for HeLa cells, they were 65.25, 61.27, 75.52, 72.82 µg/mL, respectively. M-Ag3PO4 nanoparticles did not inhibit HEK-293 cells. Apoptotic assay revealed that the numbers of DAPI stained cells were significantly lower in the M-Ag3PO4-treated cells versus control.
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Nanopartículas del Metal , Nanopartículas , Antibacterianos/farmacología , Bromuros/farmacología , Escherichia coli , Células HEK293 , Células HeLa , Humanos , Staphylococcus aureusRESUMEN
COVID-19, caused by the coronavirus SARS-CoV-2, emerged in late December 2019 in Wuhan, China. As of 8 April 2022, the virus has caused a global pandemic, resulting in 494,587,638 infections leading to 6,170,283 deaths around the world. Although several vaccines have received emergency authorization from USA and UK drug authorities and two more in Russia and China, it is too early to comment on the prolonged effectiveness of the vaccines, their availability, and affordability for the developing countries of the world, and the daunting task to vaccinate 7 billion people of the world with two doses of the vaccine with additional booster doses. As a result, it is still worthwhile to search for drugs and several promising leads have been found, mainly through in silico studies. In this study, we have examined the binding energies of several alkaloids and anthocyanin derivatives from the Solanaceae family, a family which contains common consumable vegetables and fruit items such as eggplant, pepper, and tomatoes. Our study demonstrates that Solanaceae family alkaloids such as incanumine and solaradixine, as well as anthocyanins and anthocyanidins, have very high predicted binding energies for the 3C-like protease of SARS-CoV-2 (also known as Mpro). Since Mpro is vital for SARS-CoV-2 replication, the compounds merit potential for further antiviral research towards the objective of obtaining affordable drugs.
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Alcaloides , Tratamiento Farmacológico de COVID-19 , Solanaceae , Alcaloides/farmacología , Antocianinas , Antivirales/química , Proteasas 3C de Coronavirus , Cisteína Endopeptidasas/química , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Péptido Hidrolasas/metabolismo , Fitoquímicos/farmacología , Inhibidores de Proteasas/química , SARS-CoV-2 , Solanaceae/metabolismo , Verduras/metabolismo , Proteínas no Estructurales Virales/metabolismoRESUMEN
The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological activity studies of this plant. In this exploratory study, we show that various phytochemicals from Artemisia herba-alba can be useful against COVID-19 (in silico studies) and for its associated comorbidities. COVID-19 is a new disease, so reports of any therapeutic treatments against it (traditional or conventional) are scanty. On the other hand, we demonstrate, using Artemisia herba-alba as an example, that through a proper search and identification of medicinal plant(s) and their phytochemicals identification using secondary data (published reports) on the plant's ethnic uses, phytochemical constituents, and pharmacological activities against COVID-19 comorbidities and symptoms coupled with the use of primary data obtained from in silico (molecular docking and molecular dynamics) studies on the binding of the selected plant's phytochemicals (such as: rutin, 4,5-di-O-caffeoylquinic acid, and schaftoside) with various vital components of SARS-CoV-2, it may be possible to rapidly identify plants that are suitable for further research regarding therapeutic use against COVID-19 and its associated symptoms and comorbidities.
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Artemisia/química , Tratamiento Farmacológico de COVID-19 , Extractos Vegetales/química , Extractos Vegetales/farmacología , COVID-19/epidemiología , Comorbilidad , Proteasas 3C de Coronavirus/química , Etnobotánica/métodos , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fitoquímicos/química , Plantas Medicinales/químicaRESUMEN
Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague-Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) â 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) â 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.
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Analgésicos Opioides/farmacología , Conducta Animal/efectos de los fármacos , Morfina/farmacología , Actividad Motora/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Masculino , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
Background and Aim: Milk, a nutritious food, is widely consumed in human diets; however, contamination by micro-organisms can negatively impact its quality and consumer health. Contamination by micro-organisms affects the quality of milk, which can affect the quality of the milk production chain. This study aimed to determine the changes in milk composition and antibiotic susceptibility related to bacteria isolated from dairy cow milk. Materials and Methods: Raw milk samples were collected from 72 dairy cows. All milk samples were subjected to the California Mastitis Test (CMT) for CMT score determination. We also investigated milk composition, bacterial culture (BC), and antibiotic susceptibility. Results: About 47.22% and 30.56% of dairy cattle were positive for CMT + BC and automatic somatic cell count (ASCC) + BC, respectively. Fecal appearance and animal age were found to be risk factors for ASCC + BC positivity in dairy cattle. Bacteria were found in approximately 76% of milk samples, with the most common isolated species being α-hemolytic Streptococcus spp., coagulase-negative Staphylococcus spp., and Escherichia coli. Of these, 70% are resistant to at least one antibiotic. Variation in the multidrug resistance pattern was high in Klebsiella spp. Conclusions: Fecal appearance and animal age are risk factors for ASCC + BC positivity in dairy cattle. This study identified antibiotic and multidrug resistance patterns, which require comprehensive studies and effective surveillance systems. Remarkably, the use of antibiotic therapy in dairy cattle should be monitored.
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INTRODUCTION: Toxoplasma gondii is an obligate intracellular parasite affecting a broad range of warm-blooded animals, including humans. Infection acquired during pregnancy can be transmitted to the fetus and leading to serious problems such as spontaneous abortion, stillbirth, or severe mental and/or physical handicaps in the child. The purpose of this study was to investigate the seroprevalence of Toxoplasma infection and related risk factors in pregnant woman. METHODOLOGY: The study enrolled 1200 serum samples of pregnant women from February-November 2017. Then the samples were tested for the presence of anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. RESULTS: Out of the 1200 samples, 381 (31.7%) and 41 (3.4%) subjects were positive for IgG and IgM Ab, respectively. Among the evaluated risk factors, the seroprevalence of Toxoplasma infection was not related to the occupation in a significant way. However significant relationship was observed with factors such as; contact with soil, cats, consumption of raw washed vegetables, and washed hands before meals. CONCLUSIONS: According to the results, more than two-thirds of pregnant women are susceptible to Toxoplasma infection, hence training health care programs should be provided to prevent infection.
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Aborto Espontáneo , Toxoplasma , Toxoplasmosis , Animales , Niño , Humanos , Femenino , Embarazo , Mujeres Embarazadas , Estudios Seroepidemiológicos , Anticuerpos Antiprotozoarios , Inmunoglobulina G , Estudios Transversales , Toxoplasmosis/epidemiología , Factores de Riesgo , Inmunoglobulina MRESUMEN
Cysticercus fasciolaris (C. fasciolaris) is the larval stage of a cestode parasite named Taenia taeniaeformis (T. taeniaeformis). C. fasiolaris is found in small rodents, especially rats. Rattus species are listed as intermediate hosts of this parasite, and cats are the main definitive host of C. fasiolaris. The objective of this study was to study the pathological, microscopic, and molecular aspects of C. fasciolaris in rodents residing in human residence areas. One hundred and two rodents were trapped in human settlements and dissected for larva-containing cyst examinations in the body cavity. The larvae of C. fasciolaris were investigated using histopathological examination, microscopic observations under a stereomicroscope and scanning electron microscope, and molecular detection using polymerase chain reaction. The prevalence of hepatic cysts containing larvae was 8.91% (95% CI = 4.16-16.24). In addition, the older larvae also had longer micropapillae. Histopathological investigation revealed normal hepatic tissue containing larvae and a scanty fluid cyst. The cyst capsule contains mostly mononuclear cells and spindle cells in all infected rats. The molecular detection using two primer sets revealed the amplicons were similar to the clade of C. fasciolaris. In the future, more investigation is necessary to fully understand the parasite's molecular pathogenesis and virulent molecules, which are less obvious.
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Quistes , Taenia , Ratas , Humanos , Animales , Cysticercus , Tailandia/epidemiología , Taenia/genética , Roedores , Larva , Quistes/veterinariaRESUMEN
Garcinia mangostana extract (GME) has severe pharmacokinetic deficiencies and is made up of a variety of bioactive components. GME has proven its anti-Acanthamoeba effectiveness. In this investigation, a GME-loaded niosome was developed to increase its potential therapeutic efficacy. A GME-loaded niosome was prepared by encapsulation in a mixture of span60, cholesterol, and chloroform by the thin film hydration method. The vesicle size, zeta potential, percentage of entrapment efficiency, and stability of GME-loaded niosomes were investigated. The values for GME-loaded niosome size and zeta potential were 404.23 ± 4.59 and -32.03 ± 0.95, respectively. The delivery system enhanced the anti-Acanthamoeba activity, which possessed MIC values of 0.25-4 mg mL-1. In addition, the niosomal formulation decreased the toxicity of GME by 16 times. GME-loaded niosome must be stored at 4 °C, as the quantity of remaining GME encapsulated is greater at this temperature than at room temperature. SEM revealed the damage to the cell membrane caused by trophozoites and cysts, which led to dead cells. In light of the above, it was found that GME-loaded niosomes had better anti-Acanthamoeba activity. The study suggested that GME-loaded niosomes could be used as an alternative to Acanthamoeba's therapeutic effects.
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The emergence of antibiotic-resistant bacteria and hospital-acquired bacterial infection has become rampant due to antibiotic overuse. Virulence factors are secondary to bacterial growth and are important in their pathogenesis, and therefore, new antimicrobial therapies to inhibit bacterial virulence factors are becoming important strategies against antibiotic resistance. Here, we focus on anti-virulence factors that act through anti-quorum sensing and the subsequent clearance of bacteria by antimicrobial compounds, especially active herbal extracts. These quorum sensing systems are based on toxins, biofilms, and efflux pumps, and bioactive compounds isolated from medicinal plants can treat bacterial virulence pathologies. Ideally, bacterial virulence factors are secondary growth factors of bacteria. Hence, inhibition of bacterial virulence factors could reduce bacterial pathogenesis. Furthermore, anti-virulence factors from herbal compounds can be developed as novel treatments for bacterial infection. Therefore, this narrative review aims to discuss bacterial virulence factors acting through quorum sensing systems that are preserved as targets for treating bacterial infection by plant-derived compounds.
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Trypanosomes are blood parasites infected in various mammals, including rats. The presence of rats in human settlements can increase the chance of Trypanosoma transmission to humans. The molecular study of multispacer in Trypanosoma spp. in naturally infected rodents in Thailand is scanty. The objective of this study was to detect Trypanosoma in the blood of the captured rats in Nakhon Si Thammarat, Thailand, using microscopic and molecular techniques. This was a cross-sectional study conducted in human settlement areas. Ninety-nine blood samples were collected using cardiac puncture. A blood sample was smeared on a glass slide and examined using a compound light microscope and a scanning electron microscope. Moreover, polymerase chain reaction was applied to detect Trypanosoma evansi and T. lewisi in the blood. An additional primer set was used to confirm the species of the detected trypanosome. Approximately 18% of the rats had positive Trypanosoma infections. All Trypanosoma-positive blood samples were matched with sequences of T. lewisi. The stumpy form of trypanosome had higher nucleus related parameters than the slender form. Interestingly, the partial sequences of the alpha-tubulin gene of T. lewisi were first reported in the naturally infected RrC in this study. Based on the results obtained, T. lewisi biology, particularly the virulent components and route of transmission, pathogenesis, and in vitro experiments, are strongly recommended for further study.
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Trypanosoma lewisi , Trypanosoma , Tripanosomiasis , Humanos , Ratas , Animales , Trypanosoma lewisi/genética , Tailandia/epidemiología , Tripanosomiasis/epidemiología , Tripanosomiasis/veterinaria , Tripanosomiasis/diagnóstico , Estudios Transversales , Trypanosoma/genética , RoedoresRESUMEN
Extended-spectrum beta-lactamase (ESBL) production and biofilm formation are mechanisms employed by Escherichia coli to resist beta-lactam antibiotics. Thus, we aimed to examine antibiotic resistance associated with ESBL production and biofilm formation in E. coli isolates from swine farms in Southern Thailand. In total, 159 E. coli isolates were obtained, with 44 isolates identified as ESBL producers, originating from feces (18.87 %) and wastewater (8.80 %) samples. All ESBL-producing strains exhibited resistance to ampicillin (100 %), followed by the cephalosporin group (97.73 %) and tetracycline (84.09 %). Multidrug resistance was observed in 17 isolates (38.63 %). Among the isolates from feces samples, the blaGES gene was the most prevalent, detected in 90 % of the samples, followed by blaCTX-M9 (86.67 %) and blaCTX-M1 (66.67 %), respectively. In the bacteria isolated from wastewater, both blaGES and blaCTX-M9 genes were the predominant resistance genes, detected in 100 % of the isolates, followed by blaCTX-M1 (64.29 %) and blaTEM (50 %), respectively. Strong biofilm formation was observed in 11 isolates (36.67 %) from feces and 4 isolates (25.57 %) from wastewater samples. Notably, nearly 100 % of ESBL-producing strains isolated from feces tested positive for both pgaA and pgaC genes, which play a role in intracellular adhesion and biofilm production. These findings contribute to the understanding and potential control of ESBL-producing E. coli, and the dissemination of antibiotic resistance and biofilm-related genes in swine farms.
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Infecciones por Escherichia coli , Proteínas de Escherichia coli , Enfermedades de los Porcinos , Animales , Porcinos , Escherichia coli , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/veterinaria , Aguas Residuales , beta-Lactamasas/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Biopelículas , Proteínas de la Membrana Bacteriana ExternaRESUMEN
Fermented foods have been used over the centuries in various parts of the world. These foods are rich in nutrients and are produced naturally using various biological tools like bacteria and fungi. Fermentation of edible foods has been rooted in ancient cultures to keep food for preservation and storage for a long period of time with desired or enhanced nutritional values. Inflammatory diseases like rheumatoid arthritis, osteoarthritis, and chronic inflammatory pain are chronic disorders that are difficult to treat, and current treatments for these disorders fail due to various adverse effects of prescribed medications over a long period of time. Fermented foods containing probiotic bacteria and fungi can enhance the immune system, improve gastrointestinal health, and lower the risk of developing various inflammatory diseases. Foods prepared from vegetables by fermentation, like kimchi, sauerkraut, soy-based foods, or turmeric, lack proper clinical and translational experimental studies. The current review has focused on the effectiveness of various fermented foods or drinks used over centuries against inflammation, arthritis, and oxidative stress. We also described potential limitations on the efficacies or usages of these fermented products to provide an overarching picture of the research field.
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Alimentos Fermentados , Probióticos , Alimentos de Soja , Alimentos Fermentados/microbiología , Probióticos/uso terapéutico , Verduras/microbiología , Bacterias , FermentaciónRESUMEN
This study aimed to assess antibacterial activity of Knema retusa wood extract (KRe) against antibiotic resistant staphylococci which are causative agents of bovine mastitis. From 75 cases of intramammary infections in dairy cows, 66 staphylococcal isolates were collected, including 11 Staphylococcus aureus isolates (17%) and 55 coagulase-negative staphylococci (83%). Sixty isolates (91%) formed strong biofilms. KRe had minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) against the isolates ranging 32-256 ug/mL and 64-512 ug/mL, respectively. Two-hour KRe exposures at 4×MIC, viabilities of S. aureus and S. haemolyticus decreased by 3 log10 compared to the control. Scanning EM (SEM) showed that KRe disrupted the bacterial cells of both species. KRe at 1/16×MIC significantly inhibited biofilm formation (P < 0.05) in both S. aureus and S. haemolyticus. At 1/2×MIC, S. aureus and S. haemolyticus biofilm inhibition ranged from 75 to 99%. Cells within established biofilms were disrupted 66-83% by KRe at 32×MIC. Moreover, 1/2×MIC KRe reduced bacterial adhesion to glass surfaces observed by SEM. According to GC-MS analysis, the major compound in KRe was endo-2-hydroxy-9,9-(ethylenedioxy)-1-carbethoxy bicyclo [3.3.1] nonane (E2N). Molecular docking analysis of E2N has a high affinity for staphylococcal accessory regulator A (SarA), binding free-energy - 6.40kcal/mol. The results suggested that KRe may have medicinal benefits by inhibiting the growth, biofilm, and adhesion of antibiotic resistant staphylococci isolated from bovine mastitis.
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Enfermedades de los Bovinos , Mastitis Bovina , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Bovinos , Femenino , Animales , Staphylococcus aureus , Mastitis Bovina/tratamiento farmacológico , Mastitis Bovina/microbiología , Antibacterianos/farmacología , Simulación del Acoplamiento Molecular , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Staphylococcus , Biopelículas , Pruebas de Sensibilidad Microbiana/veterinariaRESUMEN
The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2.
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Analgesic tolerance is a major problem in the clinic for the maintenance of opioid-induced long-term pain relief. Opioids with mixed activity on multiple opioid receptors promise reduced antinociceptive tolerance in preclinical studies, but these compounds typically show poor bioavailability upon oral, subcutaneous, intraperitoneal, or intravenous administration. We designed UTA1003 as a novel opioid that acts as a mu (MOP) and kappa (KOP) opioid receptor agonist and a partial agonist for delta (DOP) opioid receptor. In the present study, its antinociceptive effects, as well as its effects on antinociceptive tolerance and motor behaviour, were investigated in male rats. Acute antinociception was measured before (basal) and at different time points after subcutaneous injection of UTA1003 or morphine using the tail flick and hot plate assays. Various motor behavioural activities, including horizontal locomotion, rearing, and turning, were automatically measured in an open-field arena. The antinociceptive and behavioural effects of repeated administration of UTA1003 and morphine were determined over eight days. UTA1003 induced mild antinociceptive effects after acute administration but induced no tolerance after repeated treatment. Importantly, UTA1003 co-treatment with morphine prevented antinociceptive tolerance compared to morphine alone. UTA1003 showed less motor suppression than morphine in both acute and sub-chronic treatment regimens, while it did not affect morphine-induced motor suppression or hyper-excitation. Based on these activities, we speculate that UTA1003 crosses the blood-brain barrier after subcutaneous administration and, therefore, could be developed as a lead molecule to avoid opioid-induced antinociceptive tolerance and motor suppression. Further structural modifications to improve its antinociceptive effects, toxicity profile, and ADME parameters are nevertheless required.
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Diagnostic approaches capable of ultrasensitive pathogen detection from low-volume clinical samples, running without any sophisticated instrument and laboratory setup, are easily field-deployable, inexpensive, and rapid, and are considered ideal for monitoring disease progression and surveillance. However, standard pathogen detection methods, including culture and microscopic observation, antibody-based serologic tests, and primarily polymerase chain reaction (PCR)-oriented nucleic acid screening techniques, have shortcomings that limit their widespread use in responding to outbreaks and regular diagnosis, especially in remote resource-limited settings (RLSs). Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based programmable technology has emerged to challenge the unmet criteria of conventional methods. It consists of CRISPR-associated proteins (Cas) capable of targeting virtually any specific RNA or DNA genome based on the guide RNA (gRNA) sequence. Furthermore, the discovery of programmable trans-cleavage Cas proteins like Cas12a and Cas13 that can collaterally damage reporter-containing single-stranded DNA or RNA upon formation of target Cas-gRNA complex has strengthened this technology with enhanced sensitivity. Current advances, including automated multiplexing, ultrasensitive single nucleotide polymorphism (SNP)-based screening, inexpensive paper-based lateral flow readouts, and ease of use in remote global settings, have attracted the scientific community to introduce this technology in nucleic acid-based precise detection of bacterial and viral pathogens at the point of care (POC). This review highlights CRISPR-Cas-based molecular technologies in diagnosing several tropical diseases, namely malaria, zika, chikungunya, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV-AIDS), tuberculosis (TB), and rabies.
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Background and Aim: Bacillus cereus and Staphylococcus aureus cause foodborne intoxication in humans and animals. Pathogens can produce biofilms controlled by the quorum sensing system. The study aimed to investigate the antibacterial, antibiofilm, and anti-quorum sensing activities of Coffea canephora P. ex Fr. (Robusta coffee) extracts against B. cereus and S. aureus. Materials and Methods: Ethanol extracts of fruit peels and seeds of Robusta coffee were tested for antibacterial activity against B. cereus and S. aureus using a broth microdilution assay. Reduction of the biofilm formation and elimination of the viability of mature biofilm-grown cells of B. cereus and S. aureus were determined. Inhibition of quorum sensing activity in Chromobacterium violaceum by the extracts was investigated using the disk diffusion method and flask incubation assay. Results: Fresh fruit peel extract showed the strongest antibacterial activity against B. cereus and S. aureus with minimum inhibitory concentration (MIC) values of 2 and 4 mg/mL, respectively. However, the extracts did not inhibit Escherichia coli, avian pathogenic E. coli, and Pseudomonas aeruginosa at 8 mg/mL. Significant inhibition of biofilm formation at 1/2 × MIC of the fresh peel extract was detected in B. cereus (56.37%) and S. aureus (39.69 %), respectively. At 8 × MIC of the fresh peel extract, a significant elimination of the mature biofilm viability was detected in B. cereus (92.48%) and S. aureus (74.49%), respectively. The results showed that fresh and dried peel fruit extracts at 1/2 × MIC significantly reduced violacein production with the highest percentage inhibition ranging from 44.53 to 47.48% at 24 h (p ≤ 0.05). Conclusion: The results of the present study suggest the potential therapeutic benefits of Robusta coffee extracts in inhibiting the growth, biofilm, and quorum sensing of both B. cereus and S. aureus. The results put forward an alternative strategy to control the foodborne intoxications caused by both pathogens.
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Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce long-term antitumor memory, causing tumor regression, eradicate minimal residual illness, and prevent non-specific or unpleasant effects. These vaccines can assist in the elimination of cancer cells from various organs or organ systems in the body, with minimal risk of tumor recurrence or metastasis. Vaccines and antigens for anticancer therapy are discussed in this review, including current vaccine adjuvants and mechanisms of action for various types of vaccines, such as DNA- or mRNA-based cancer vaccines. Potential applications of these vaccines focusing on their clinical use for better therapeutic efficacy are also discussed along with the latest research available in this field.