Acinetobacter baumannii: An overview of emerging multidrug-resistant pathogen.

The emergence of infections caused by Acinetobacter baumannii, a multidrug-resistant bacterium, has been a concern worldwide. This bacterium is an important hospitalacquired pathogen that causes several diseases including ventilator-associated pneumonia, bloodstream infections, and meningitis. This study aimed to determine antibioticresistant mechanisms in the pathogenesis of A. baumannii and the alternative treatment strategies against it. The combined actions of outer membrane protein A, formation of a biofilm on biotic and abiotic surfaces, phospholipases C and D, metal homeostatic system, lipopolysaccharides, and verotoxins are relevant for virulence and pathogenesis. A. baumannii resists the broad-spectrum antibiotics by its mechanisms of resistance, such as ß-lactamases, efflux pump, aminoglycoside modifying enzymes, permeability changes, and alternation of targets. In an attempt to overcome the resistance mechanisms, plant-derived compounds and a combination of the antibiotics and the plant phytocompounds have been focused. Nanoparticles synthesised with the plant extract have been studied extensively. Furthermore, we projected modern methods, including multi-omics analysis, to study insight into mechanisms of actions of antibiotics. The information suggested that the potential antibiotic mechanisms of A. baumannii could lead to an alternative treatment against A. baumannii infections.

Can Costus afer be used for co-treatment of COVID-19, its symptoms and comorbidities? A novel approach for combating the pandemic and implications for sub-Saharan Africa.

Despite the huge loss of lives and massive disruption of the world economy by the COVID -19 pandemic caused by SARS -CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease . Several vaccines have obtained 'emergency approval ', but difficulties are being faced in the even distribution of vaccines amongst high- and low- income countries . On top of it, comorbidities associated with COVID -19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate . This is more so in the context of sub -Saharan African and south Asian countries . Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID -19 and comorbidities . Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components - Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock V ina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and /or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ± -terpinene, making them potential therapeutics for COVID -19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID -19 and comorbidities like especially diabetes and malaria .

Can Costus afer be used for co-treatment of COVID-19, its symptoms and comorbidities? A novel approach for combating the pandemic and implications for sub-Saharan Africa

@#Despite the huge loss of lives and massive disruption of the world economy by the COVID-19 pandemic caused by SARS-CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease. Several vaccines have obtained ‘emergency approval’, but difficulties are being faced in the even distribution of vaccines amongst high- and lowincome countries. On top of it, comorbidities associated with COVID-19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate. This is more so in the context of sub-Saharan African and south Asian countries. Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID-19 and comorbidities. Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components – Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock Vina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and/or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ±-terpinene, making them potential therapeutics for COVID-19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID-19 and comorbidities like especially diabetes and malaria.

Magnesium supplementation ameliorates toxic effects of 2,4-dichlorophenoxyacetic acid in rat model.

2,4-Dichlorophenoxyacetic acid (2,4-D) is an extensively used herbicide in the field of agriculture, its ever-escalating use induces toxicity, health effects, and environmental impact. Oxidative stress plays a key role in pathogenesis of 2,4-D-induced liver and kidney damage. Magnesium (Mg) is a highly effective antioxidant agent in restoring oxidative damage by directly influencing the metabolic and physiological processes. Therefore, the present study aimed to evaluate Mg role in ameliorating the oxidative damages provoked by 2,4-D in rat model. Male Wistar rats (180-220 g) were distributed into four groups and treated intragastrically for 4 weeks. Group 1: control, group 2: 2,4-D (150 mg/kg body weight/day), group 3: simultaneously treated with 2,4-D (150 mg/kg body weight/day) and Mg supplement (50 mg/kg body weight/day), and group 4: Mg supplement (50 mg/kg body weight/day). Under experimental conditions, plasma hepatic and renal biomarkers, tissue oxidative status, and antioxidant enzymes activities were investigated. Results demonstrated that 2,4-D intoxication caused hepatic and renal impairments as indicated by the significantly increased (p < 0.001) alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, and blood urea nitrogen levels. In addition, 2,4-D caused a significant enhancement (p < 0.001) in the level of malondialdehyde as well as reduction (p < 0.001) of the superoxide dismutase, catalase, and glutathione reductase activities in both hepatic and renal tissues. Mg treatment prevented and reversed the toxic variations induced by 2,4-D. In general, these outcomes suggest that Mg may have antioxidant potential and ameliorative effects against 2,4-D provoking hepatic and renal toxicity in rat model.

Zika virus modulates blood-brain barrier of brain microvascular endothelial cells.

Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.

Zika virus modulates blood-brain barrier of brain microvascular endothelial cells

@#Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.

Role of peroxisome proliferator-activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus.

The present study focused on the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i.p. 35 mg/kg); group 5: T2DM rats treated with RSG (3 mg/kg orally for 7 days). Serum levels of AGEs and visfatin, renal damage, and oxidative stress were analyzed. Results showed that HFD-induced obesity and T2DM caused an elevated blood glucose, serum AGEs, visfatin, insulin, urea, creatinine, and tissue malondialdehyde, whereas a decreased catalase and superoxide dismutase activity were observed. The PPAR-γ activation via agonist restored these changes. Our findings suggest that AGEs and visfatin possess an important role in the progression of renal oxidative stress, which can be reduced by the PPAR-γ agonist that impede deleterious effects of HFD and HFD-induced T2DM on renal damage.

Soil-Transmitted Helminths in Malaysia landscape: an aborigines study.

Soil-transmitted helminths (STH) is a group of parasitic nematodes, including Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus, which can cause gastrointestinal disorders in humans. STH is prevalent among neglected communities in both developing and developed countries. This present study aims to determine the current prevalence of STH infections in Aboriginal population after mass delivering of antihelminthic drugs was proposed by WHO in 2005 and a health education learning package (HELP) was initiated in Malaysia in 2012. A total of 235 human fecal samples were collected and a pre-tested questionnaire was given to gather information about the socio-demographic of the Aborigine communities living in Kedah and Selangor, Malaysia. The samples were screened by a direct-fecal smear and confirmed by formalin-ether sedimentation methods. From human faeces, 81.7% was found to be infected with one or more STH species. T. trichiura was the most commonly detected (76.6%), followed by hookworms (26.4%) and A. lumbricoides (19.1%). Triple infections were found in 6.4% of the studied population. Univariate analysis showed that individuals with age group, male, presence of indoor toilet, family size with <7 members and bad living habits (i.e., without antihelminthic drugs) were significantly associated with STH infections. The analysis further showed that walking barefoot was the significant contributing factor to hookworm infections. The high prevalence of human STH infections is alarming. Thus, the urgency in implementing health education related behavioral practice and hygiene to reduce disease burden in these rural communities are a crucial need.

Soil-Transmitted Helminths in Malaysia landscape: an aborigines study

Soil-transmitted helminths (STH) is a group of parasitic nematodes, including Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus, which can cause gastrointestinal disorders in humans. STH is prevalent among neglected communities in both developing and developed countries. This present study aims to determine the current prevalence of STH infections in Aboriginal population after mass delivering of antihelminthic drugs was proposed by WHO in 2005 and a health education learning package (HELP) was initiated in Malaysia in 2012. A total of 235 human fecal samples were collected and a pre-tested questionnaire was given to gather information about the socio-demographic of the Aborigine communities living in Kedah and Selangor, Malaysia. The samples were screened by a direct-fecal smear and confirmed by formalin-ether sedimentation methods. From human faeces, 81.7% was found to be infected with one or more STH species. T. trichiura was the most commonly detected (76.6%), followed by hookworms (26.4%) and A. lumbricoides (19.1%). Triple infections were found in 6.4% of the studied population. Univariate analysis showed that individuals with age group, male, presence of indoor toilet, family size with <7 members and bad living habits (i.e., without antihelminthic drugs) were significantly associated with STH infections. The analysis further showed that walking barefoot was the significant contributing factor to hookworm infections. The high prevalence of human STH infections is alarming. Thus, the urgency in implementing health education related behavioral practice and hygiene to reduce disease burden in these rural communities are a crucial need.

Titiwangsa Lake a source of urban parasitic contamination.

Urban recreational lake acts as a source of waterborne parasites contamination, as reported in 2013 in Petaling Jaya, Selangor, Malaysia. This scenario will lead to the transmission of waterborne diseases due to exposure of water-related activities by humans. This study was conducted to reveal the occurrence of common waterborne parasites in a urban lake (i.e. Titiwangsa Lake). The lake is situated in the city of Kuala Lumpur and is known to be overcrowded with vast activities participated by both local and tourist. Results of study showed the presence of Cryptosporidium, Giardia, free-living amoeba, and helminthlike ova from the lake.

Titiwangsa Lake a source of urban parasitic contamination

Urban recreational lake acts as a source of waterborne parasites contamination, as reported in 2013 in Petaling Jaya, Selangor, Malaysia. This scenario will lead to the transmission of waterborne diseases due to exposure of water-related activities by humans. This study was conducted to reveal the occurrence of common waterborne parasites in a urban lake (i.e. Titiwangsa Lake). The lake is situated in the city of Kuala Lumpur and is known to be overcrowded with vast activities participated by both local and tourist. Results of study showed the presence of Cryptosporidium, Giardia, free-living amoeba, and helminthlike ova from the lake.

A preliminary screening of potentially antimalarial plants against Plasmodium falciparum in vitro.

Plasmodium is a blood protozoan parasite that is responsible for malaria. To date, Plasmodium falciparum has shown multi-drug resistance, particularly in Thailand, Myanmar and Malaysia. The aim of the study is to screen the plant extracts that can effectively inhibit P. falciparum 3D7, a common lab strain malaria parasite. Nine plants were collected and processed through maceration using hexane, chloroform and ethanol, resulting in 24 crude plant extracts. Of these, extracts from Artabotrys crassifolius, Pericampylus glacus and Leuconotis eugeniifolia showed promising antiplasmodial activities at IC50 of 15.32 to 39.75 µg/mL in a modified schizont maturation assay. Further studies are warranted to explore its efficacies and lead compounds of these three plant extracts for the development of antiplasmodial drugs.

A preliminary screening of potentially antimalarial plants against Plasmodium falciparum in vitro

Plasmodium is a blood protozoan parasite that is responsible for malaria. To date, Plasmodium falciparum has shown multi-drug resistance, particularly in Thailand, Myanmar and Malaysia. The aim of the study is to screen the plant extracts that can effectively inhibit P. falciparum 3D7, a common lab strain malaria parasite. Nine plants were collected and processed through maceration using hexane, chloroform and ethanol, resulting in 24 crude plant extracts. Of these, extracts from Artabotrys crassifolius, Pericampylus glacus and Leuconotis eugeniifolia showed promising antiplasmodial activities at IC50 of 15.32 to 39.75 μg/mL in a modified schizont maturation assay. Further studies are warranted to explore its efficacies and lead compounds of these three plant extracts for the development of antiplasmodial drugs.

Electrolyte content of serum, erythrocyte, kidney and heart tissue in salt induced hypertensive rats.

The effect of salt load on the systolic blood pressure (SBP) and electrolyte levels of serum, erythrocyte, kidney and heart tissue was studied in rats. NaCl treatment increased sodium (5.69 +/- 0.4 mmol/L p < 0.001, 149.8 +/- 4.0 mEq/L, p < 0.001) and decreased potassium (112.6 +/- 2.4 mmol/L p < 0.001, 5.0 +/- 0.2 mEq/L, p < 0.001) in red cell and serum respectively. A decreased level of serum magnesium (1.4 +/- 0.3 mEq/L, p < 0.005) was observed. Sodium content was increased in both heart (39.93 +/- 2.9 mumol/g, p = n.s) and kidney tissues (44.39 +/- 0.5 mumol/g, p < 0.001). A pronounced increase in intracellular calcium (2.54 +/- 0.2 mumol/g, p < 0.001) and a decrease of magnesium content (6.05 +/- 0.8 mumol/g, p < 0.001) was observed in kidney tissue after treatment. The results suggested that marked changes in electrolyte levels of erythrocytes, serum, heart and kidney tissues in NaCl loaded rats may play a definite role in the development of salt induced hypertension.

Stress and hypertension: role of serum, red cell and tissue electrolytes.

The role of stress in the precipitation of hypertension is often described in clinical studies, although the underlying mechanism remains unknown. The present study concerns the role of electrolytes in stress induced hypertension in rats. Acute immobilization stress of one hour elevated systolic blood pressure (SBP) in rats. Restraint induced blood pressure elevation was associated with increased sodium concentration in the red cells, heart and kidney, and decreased potassium in the red cells. Magnesium concentration increased and calcium concentration decreased in the serum. Increases of calcium and decreases of magnesium were also observed in the heart and kidney tissues. The results may help toward an understanding of the relationship between hypertension and electrolyte homeostasis. A possible role of Na(+)-K(+)-ATPase activity leading to observed changes of electrolytes or vice versa is discussed.

Effect of NSAIDS on serum electrolytes and osmolality.

Rabbits and rats were injected two Nonsteroidal anti-inflammatory drugs (aspirin 300 mg/kg or indomethacin 3 mg/kg) intraperitoneally. One hour after injection blood was analyzed for serum electrolytes and osmolality. Administration of both aspirin and indomethacin in rabbits and rats caused increase in serum sodium, potassium, calcium, chloride, magnesium, phosphorus and osmolality. Results suggest the marked similarity in the action of aspirin and indomethacin on electrolytes and osmolality. It is concluded that the ingestion of aspirin and indomethacin can have a major effect on serum electrolytes and osmolality that may influence the interpretation of clinical data in patients taking these drugs.

Effect of ethanol on serum electrolytes and osmolality.

Rats and rabbits were injected ethanol 2 g/kg intraperitoneally. One hour after injection blood was analyzed for serum electrolytes and osmolality. Administration of ethanol caused decrease in serum sodium (p less than 0.0005), potassium (p less than 0.0005), calcium (p less than 0.0005), chloride (p less than 0.005), magnesium (p less than 0.0005) in rabbits. Further studies of intraperitoneal administration of ethanol in rats showed decrease in concentration of sodium (p less than 0.025), potassium (p less than 0.025), calcium (p less than 0.01) chloride (p less than 0.005) magnesium (p less than 0.005), phosphorus (p less than 0.025) and glucose (p less than 0.005). Administration of ethanol caused an increase in serum osmolality in both rabbits and rats (p less than 0.005, p less than 0.05). It is concluded that ethanol ingestion is probably the commonest cause of the hyperosmolar state. Although the osmotic and sedative effects of ethanol are pharmacologically unrelated, the presence of ethanol should be considered in comatose patients in whom the measured plasma osmolality appreciably exceeds that predicted on the basis of plasma glucose, urea and electrolytes concentration.