Affecting Humans Worldwide Research Articles

Comparative Analysis of Virulence Mechanisms of Trypanosomatids Pathogenic to Humans.

Trypanosoma brucei, Leishmania spp., and T. cruzi are flagellate protozoans of the family Trypanosomatidae and the causative agents of human African trypanosomiasis, leishmaniasis, and Chagas disease, respectively. These diseases affect humans worldwide and exert a significant impact on public health. Over the course of evolution, the parasites associated with these pathologies have developed mechanisms to circumvent the immune response system throughout the infection cycle. In cases of human infection, this function is undertaken by a group of proteins and processes that allow the parasites to propagate and survive during host invasion. In T. brucei, antigenic variation is promoted by variant surface glycoproteins and other proteins involved in evasion from the humoral immune response, which helps the parasite sustain itself in the extracellular milieu during infection. Conversely, Leishmania spp. and T. cruzi possess a more complex infection cycle, with specific intracellular stages. In addition to mechanisms for evading humoral immunity, the pathogens have also developed mechanisms for facilitating their adhesion and incorporation into host cells. In this review, the different immune evasion strategies at cellular and molecular levels developed by these human-pathogenic trypanosomatids have been discussed, with a focus on the key molecules responsible for mediating the invasion and evasion mechanisms and the effects of these molecules on virulence.

Molecular detection and identification of Babesia bovis and Trypanosoma spp. in one-humped camel (Camelus dromedarius) breeds in Egypt.

Background and Aim:Camels are a unique source of milk and meat, which helps recover from several diseases that affect humans worldwide. In Egypt, one of the great obstacles for this industry is tick-borne diseases. This study aimed to characterize blood parasite infections, such as Babesia (B.) bovis and Trypanosoma (T.) spp. in one-humped camel (Camelus dromedarius) (n=142) breeds in Halayeb and Shalateen, Egypt, through phylogenetic analysis.Materials and Methods:The prevalence of B. bovis and Trypanosoma spp. was identified in camels using polymerase chain reaction (PCR) assays targeting the Rhoptry-Associated Protein-1 and internal transcribed spacer 1 genes, respectively. A nested PCR technique was conducted to detect B. bovis. At the same time, KIN multispecies PCR assay was employed to diagnose and classify trypanosome DNA in camels.Results:B. bovis was detected in 4/142 camels with an infection rate of 2.81%. Sequencing and phylogenetic analyses revealed that the strain of B. bovis isolated from this population was closely related to strains isolated from Argentine, the United States, and Brazil. Moreover, Trypanosoma evansi was detected in 8/142 camels with an infection rate of 5.63%. Sequencing and phylogenetic analyses revealed that this isolated strain T. evansi was closely related to Trypanosoma theileri detected from cattle in Brazil.Conclusion:The obtained data indicated the existence of B. bovis and T. evansi in camels from two provinces of Egypt. The obtained findings have economic significance and reflect the importance of implementing effective prevention and control methods across Egypt to reduce the incidence of B. bovis and T. evansi in camels.

Field Evaluation of Selected Common Household Containers as Oviposition Attractants of <em>Aedes Albopictus</em> (Diptera: Culicidae

Dengue is a fatal arthropod-borne disease that affects humans worldwide. The mosquito Aedes albopictus (Skuse) is the secondary vector of dengue in Sri Lanka, however, studies on oviposition preferences of Ae. albopictus is scarce. The objective of the current study was to investigate the oviposition attraction of Aedes albopictus to selected household containers; black colour basins, metal cans, rain gutter parts, curd pots, coconut shells and yoghurt cups. For this, water containers for oviposition were placed in three outdoor shady sites and at three different heights. The mosquito larvae were collected after 5 days. The larvae were reared to adult stage and then they were identified and enumerated. Wing lengths of adult female mosquitoes that developed in different containers were measured. In the meantime, temperature, pH, dissolved oxygen (DO) and total dissolved solids (TDS) were measured in each container. The Ae. albopictus larval density was higher in coconut shells. The maximum mean number of mosquito larvae was observed in the containers at ground level. The oviposition attraction of Ae. albopictus was increased with the aging of coconut shells and old coconut shells were preferred than new coconut shells. Highest TDS level and neutral pH were observed in coconut shells which support the mosquito oviposition. The highest wing lengths were observed in female Ae. albopictus that developed in curd pots, representing higher fecundity. In conclusion, discarded coconut shells and curd pots should be carefully managed as means of eliminating dengue vector mosquito breeding sites.

Molecular genotyping of Giardia lamblia assemblages by conventional PCR in rural and urban areas in Egypt.

Background Giardiasis is one of the most important parasitic gastro-intestinal infections that affect humans worldwide. Children are the most affected age group either in developing or developed countries. Genotyping of Giardia lamblia by molecular techniques classified it into eight assemblages; of which, assemblages A and B are potentially zoonotic pathogens. This study was done to investigate the prevalence of different Giardia lamblia genotypes by conventional PCR, and to explore the environmental and patientsʼ sociodemographic factors that may affect the disease prevalence. Methods Two hundreds fecal samples were collected at Damanhour General Hospital from patients with gastrointestinal diseases. All samples were examined microscopically, and the positive ones were investigated by conventional PCR. Results Giardiasis was detected in 92 (46%) samples. Eighty-eight samples gave positive results by PCR, 18% of which were assemblage A, 70.5% were assemblage B, and 11.5% were mixed infection of both assemblages. The infection was more prevalent in males, rural patients and the highly educated ones. Conclusions This study presents critical and demonstrative data regarding public health in Egypt. The results reveal that the prevalence of giardiasis is high among both rural and urban patients, particularly in children. It also prevails in patients of all education levels, and patients dealing and not dealing with animals. Moreover, we recommend PCR amplifying the triose phosphate isomerase (tpi) gene in fresh fecal samples as very effective method for the diagnosis and genotyping.

Therapeutic Use of Silver Nanoparticles in the Prevention and Arrest of Dental Caries.

Dental caries is one of the major diseases of the oral cavity affecting humans worldwide. Different alternatives have been used for its control, but its incidence and prevalence are still high. On the other hand, silver has been used for centuries due to its antimicrobial properties. With advances in nanotechnology, the use and research in nanomaterials has increased, recently, and silver nanoparticles have become an essential part of the dental practice, giving materials physical and chemical improvements in their properties, used for their antibacterial capacity preventing and arresting dental caries. The objective of this review was to examine the use of silver nanoparticles, in the treatment of dental caries in the remineralization of teeth hard tissues, as well as the antimicrobial potential, cytotoxicity, and long-term effectiveness.

A CNN-based active learning framework to identify mycobacteria in digitized Ziehl-Neelsen stained human tissues

Tuberculosis is the most common mycobacterial disease that affects humans worldwide. Rapid and reliable diagnosis of mycobacteria is crucial to identify infected individuals, to initiate and monitor treatment and to minimize or prevent transmission. Microscopic identification of acid-fast mycobacteria (AFB) in tissue sections is usually accomplished by examining Ziehl-Neelsen (ZN) stained slides in which AFB appear bright red against the blue background.Because the ZN-stained slides require time consuming and meticulous screening by an experienced pathologist, our team developed a machine learning pipeline to classify digitized ZN-stained slides as AFB-positive or AFB-negative. The pipeline includes two convolutional neural network (CNN) models to recognize tiles containing AFB, and a logistic regression (LR) model to classify slides based on features from AFB-probability maps assembled from the CNN tile-based classification results. The first CNN was trained using tiles from 6 AFB-positive and 8 AFB-negative slides, and the second CNN was trained using the initial tile set expanded by additional tiles from 19 AFB-negative slides selected within an active learning framework. When evaluated on a separate set of tiles, the two CNNs yielded F1 scores of 99.03% and 98.75%, respectively, and were used to classify tiles in a separate set of 134 slides (46 AFB-positive and 88 AFB-negative). The classification yielded two AFB-probability maps, one for each CNN. The LR model was then 10-fold cross-validated using the average of feature vectors extracted from the AFB-probability maps generated by each CNN. The feature vector consisted of seven features of the AFB-probability map histogram and the positive tile rate (PTR). The sensitivity (87.13%), specificity (87.62%) and F1 (80.18%) achieved by this model were superior to the baseline performance of PTR-based separation of slides that yielded F1 scores of 73.13% and 66.67% in the AFB-probability maps outputted by the CNN trained within the active learning framework and the CNN trained only on the initial set of slides, respectively.Our CNNs outperformed several recently published models for AFB detection. Active learning induced robust learning of features by the CNN and led to improved LR classification performance of slides. In the 52 AFB-positive slides used in the pipeline development, the AFB were infrequent, predominantly single and only rarely found in small clusters. Our pipeline can classify slides and visualize suspected AFB-positive areas in each slide, and thus potentially facilitate evaluation of ZN-stained tissue sections for AFB.

Survival time of Leptospira kirschneri serovar Grippotyphosa under different environmental conditions.

Leptospirosis is a re-emerging zoonotic disease of high medical importance that affects humans worldwide. Humans or animals acquire an infection with pathogenic leptospires either by direct contact with infected animals or by indirect contact to contaminated environment. Survival of Leptospira spp. in the environment after having been shed via animal urine is thus a key factor to estimate the risk of infection, but not much is known about the tenacity of pathogenic leptospires. Here, the survival time of both a laboratory strain and a field strain of L. kirschneri serovar Grippotyphosa in animal urine and their tenacity while drying was investigated and compared at different temperatures (15°C-37°C). Leptospira spp. are also often found in rivers and ponds. As the infection risk for humans and animals also depends on the spreading and survival of Leptospira spp. in these environments, the survival of L. kirschneri serovar Grippotyphosa was investigated using a 50-meter-long hose system simulating a water stream. Both strains did not survive in undiluted cattle or dog urine. Comparing different temperatures and dilution media, the laboratory strain survived the longest in diluted cattle urine with a slightly alkaline pH value (3 days), whilst the field strain survived in diluted dog urine with a slightly acid pH value up to a maximum of 24 h. Both strains did not survive drying on a solid surface. In a water stream, leptospires were able to move faster or slower than the average velocity of the water due to their intrinsic mobility but were not able to survive the mechanical damage caused by running water in the hose system. From our results we conclude, that once excreted via animal urine, the leptospires immediately need moisture or a water body to survive and stay infectious.

Differential epidemiology and antibiotic resistance of lactose-fermenting and non-fermenting Escherichia coli: Is it just a matter of taste?

Urinary tract infections (UTIs) are some of the most common infections affecting humans worldwide. Occurrence of atypical, lactose non-fermenting, biochemically “inactive” strains of E. coli in clinical material has been described in the literature, which may cause a significant diagnostic challenge. The present retrospective microbiological study was carried out using isolates and data collected between January 1, 2013, and December 31, 2017, at the Institute of Clinical Microbiology. n = 24,285 positive urine samples were noted during the study period, out of which, samples positive for either lac + and lac- E. coli were included in the analysis. E. coli represented n = 7075 (55.8% ± 4.6%) of outpatient and n = 4916 (42.4% ± 3.6%) of inpatient isolates. n = 401 (3.3%; 80.2 ± 14.6/year) lac- E. coli isolates were identified from urinary tract infections. The ratio of lac- E. coli isolates was significantly higher in outpatient samples (262 vs. 139). Resistance levels of lac- isolates for antibiotics commonly used for treating UTIs were significantly higher for both inpatient and outpatient isolates: norfloxacin, ciprofloxacin, fosfomycin and nitrofurantoin. It is essential to pay attention to the presence of lac- strains, and their omission from clinical material during diagnostic procedures may have significant consequences for epidemiological studies and therapy.

Survey of entomopathogenic nematodes and associate bacteria in Thailand and their potential to control Aedes aegypti

AbstractAedes aegypti is an insect vector that transmits several viruses affecting humans worldwide. Entomopathogenic nematodes (EPNs) and their symbiotic bacteria are organisms with the potential to control many insects. In this study, we did a survey aimed to identify EPNs and their symbiotic bacteria and evaluate the larvicidal activity of bacteria against Ae. aegypti. We collected 540 soil samples from 108 sites in Phitsanulok Province, lower northern Thailand. Baiting techniques and White traps were used to isolate EPNs from soil samples. By sequencing of 28S rDNA and internal transcribed spacer regions, 51 EPN isolates were identified as Steinernema surkhetense (35 isolates), Heterorhabditis indica (14 isolates) and Heterorhabditis sp. SGmg3 (two isolates). Based on sequencing of a partial region of the recA gene, 35 isolates of Xenorhabdus were identified as Xenorhabdus stockiae, and 20 Photorhabdus isolates were identified as Photorhabdus luminescens subsp. akhurstii (10 isolates), P. luminescens subsp. hainanensis (seven isolates) and P. asymbiotica subsp. australis (three isolates). Screening for larvicidal activity of bacteria against Ae. aegypti was performed in the laboratory. Xenorhabdus WB5.4 and Xenorhabdus WB12.5, which were closely related to X. stockiae, resulted in high mortality of Ae. aegypti (99.99% and 70%, respectively) at 96 hr after exposure. Comparing with control groups, mortality of Ae. aegypti larvae was low (1.11%–6.67%) after exposure for 24–96 hr. Our findings showed the potential of X. stockiae for controlling Ae. aegypti. Further studies are needed to elucidate the mechanisms through which these bacteria kill Ae. aegypti larvae.

Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice.

Degenerative changes of the intervertebral disc (IVD) are a leading cause of disability affecting humans worldwide and has been attributed primarily to trauma and the accumulation of pathology during aging. While genetic defects have also been associated with disc degeneration, the precise mechanisms driving the initiation and progression of disease have remained elusive due to a paucity of genetic animal models. Here, we discuss a novel conditional mouse genetic model of endplate-oriented disc herniations in adult mice. Using conditional mouse genetics, we show increased mechanical stiffness and reveal dysregulation of typical gene expression profiles of the IVD in adhesion G-protein coupled receptor G6 (Adgrg6) mutant mice prior to the onset of endplate-oriented disc herniations in adult mice. We observed increased STAT3 activation prior to IVD defects and go on to demonstrate that treatment of Adgrg6 conditional mutant mice with a small molecule inhibitor of STAT3 activation ameliorates endplate-oriented herniations. These findings establish ADGRG6 and STAT3 as novel regulators of IVD endplate and growth plate integrity in the mouse, and implicate ADGRG6/STAT3 signaling as promising therapeutic targets for endplate-oriented disc degeneration.

Study on increased antimicrobial resistance among bacteria isolated from ICUs Zagazig University Hospitals

Emergence of antimicrobial resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favoring increasingly broad-spectrum empiric therapy.In this study 67 isolates were collected from patients admitted to ICUs of Zagazig University Hospitals, Sharqia, Egypt. The isolates were biochemically identified and their susceptibility to different antimicrobials were tested by Kirby-Bauer standard disk diffusion method.The results showed that the recovered bacteria had high degree of resistance to different antimicrobial classes and 86.25 % were multi drug resistance (MDR). In conclusion high rate of MDR were found in this study that necessitate strict antibiotic dispensing policy to reduce the increased antibiotic resistance.

Colloidal (-)-epigallocatechin-3-gallate vesicular systems for prevention and treatment of skin cancer: A comprehensive experimental study with preclinical investigation

Skin carcinogenesis is a common malignancy affecting humans worldwide, which could benefit from nutraceuticals as a solution to the drawbacks of conventional skin cancer treatment. (−)-epigallocatechin-3-gallate (EGCG) is a promising nutraceutical in this regard; however, it suffers chemical instability and low bioavailability resulting in inefficient delivery. Therefore, EGCG encapsulation in ultradeformable colloidal vesicular systems, namely: penetration enhancer-containing vesicles (PEVs), ethosomes and transethosomes (TEs) for topical administration has been attempted in this study to overcome the problems associated with the use of free EGCG. The prepared vesicles were characterized for their entrapment efficiency, TEM visualization, chemical compatibility, antioxidant properties, ex-vivo skin deposition, photodegradation and physical stability after storage. Most of the prepared vesicles exhibited reasonable skin deposition and preservation of the inherent antioxidant properties of EGCG with good physical stability. EGCG-loaded PEVs and TEs exhibited an inhibitory effect on epidermoid carcinoma cell line (A431) in addition to reduced tumor sizes in mice, confirmed with histopathological analysis and biochemical quantification of skin oxidative stress biomarkers; glutathione, superoxide dismutase and catalase, as well as lipid peroxidation. EGCG PEVs succeeded in offering an effective delivery system targeting skin cancer, which is worthy of further experimentation.

Inhibition of peroxiredoxin 2 suppresses Wnt/β-catenin signaling in gastric cancer

Gastric cancer (GC) is the fourth most common type of malignant tumor that affects humans worldwide, but few targeted therapies for it have been considered that are based on redox systems. Peroxiredoxin2 (Prx2) functions as a reactive oxygen species (ROS)-mediated signaling regulator that controls H2O2 in mammalian cells, and it is involved in the survival of various malignant tumors. In human GC cells, Prx2 depletion markedly reduced the β-catenin levels and expression of β-catenin target genes and proteins. Cell-based assays demonstrated that Prx2 knockdown significantly ablates the cell viability, invasive activity, and colony-forming ability of both AGS and SNU668 cells. Furthermore, an experiment using conoidinA, a Prx2 inhibitor, revealed that Prx2 inhibition can overcome 5-FU resistance in GC cells. Thus, this study suggests that Prx2 plays a crucial role in regulating Wnt/β-catenin signaling in GC cells.

Oral field cancerization: Tracking the invisible

Cancer is one of the most common diseases affecting humans worldwide, despite latest advances made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still questionable. Oral cavity is one of the commonest site for potentially malignant disorders. These pre-malignant pathologies may progress to dysplastic lesions then to invasive carcinomas.The presence of one or more mucosal areas consisting of epithelial cells that have cancer-associated genetic or epigenetic alterations.The prognosis of squamous cell carcinoma patients is adversely influenced by development of a new tumor. This review highlights the pathophysiological changes during field cancerization

Long short‐term memory networks for CSI300 volatility prediction with Baidu search volume

SummaryIntense volatility in financial markets affects humans worldwide. Therefore, relatively accurate prediction of volatility is critical. We suggest that massive data sources resulting from human interaction with the Internet may offer a new perspective on the behavior of market participants in periods of large market movements. First, we select 28 key words, which are related to finance as indicators of the public mood and macroeconomic factors. Then, those 28 words of the daily search volume based on Baidu index are collected manually, from June 1, 2006 to October 29, 2017. We apply a Long Short‐Term Memory neural network to forecast CSI300 volatility using those search volume data. Compared to the benchmark GARCH model, our forecast is more accurate, which demonstrates the effectiveness of the LSTM neural network in volatility forecasting.

GIARDIA INTESTINALIS ASSEMBLAGES AMONG EGYPTIAN SYMPTOMATIC/ASYMPTOMATIC CASES IN CAIRO

Giardia intestinalis is frequent enteric protozoa, affecting humans worldwide. Human infections aremainly caused by two genetically different assemblages call A & B. This cross-sectional study characterizedthe Giardia genotypes isolated from the stool of symptomatic and asymptomatic Egyptians inCairo and correlated these genotypes with the demographic and clinical data of the cases. Stool sampleswere collected from 389 individuals (245 complaining of gastrointestinal (GIT) symptoms and144 apparently healthy asymptomatic individuals), and microscopically examined. Positive Samplesfor G. intestinalis were molecularly characterized by Copro-nPCR targeting beta-giardin gene, andthen analyzed by RFLP for assemblage identification. Giardia was detected in 62 samples (15.9%); 53samples in symptomatic cases (21.6%) and 9 samples in asymptomatic individuals (6.25%). DNA ofpositive samples was amplified by nPCR-RFLP assays. There was a significant predominance of assemblageB among symptomatic (82.7%) and asymptomatic (77.8%) groups, while the rest of sampleshad assemblage A. Among the clinical data, only flatulence was significantly associated with Giardiainfection with assemblage B. Assemblage B is the predominant genotype found in Egypt in symptomaticand asymptomatic patients suggesting an anthropologic transmission cycle.Key Words: Giardia; genotyping; Assemblage; nPCR-RFLP; beta-giardin.

Helicobacter pylori in metabolic related diseases.

Helicobacter pylori is one of the most common gastrointestinal infection affecting humans worldwide. Hp colonizes the stomach with preferential trophism for the antrum. Hp infection is associated with the development of a chronic gastritis and subsequently with several gastric diseases such as peptic disease, gastric carcinoma and MALT lymphoma. Moreover, Helicobacter pylori infection has also been reported in literature to be associated with many other extra-gastric conditions including sideropenic anemia, thrombocytopenia, neurological, liver and cardiovascular diseases. For some conditions the association is supported by solid literature data and also by the identification of the possible physiopathogenetic mechanism involved. In other cases, the link is only reported by association studies often with conflicting results. In this context, diabetes mellitus, cardiovascular disorders and liver steatosis have all been reported to be associated with Helicobacter pylori infection. Interestingly, these conditions share many characteristics and they often overlap as they represent the expression of the so called metabolic syndrome. Aim of the review was to summarize the available data regarding the association between Helicobacter Pylori infection and diabetes mellitus, cardiovascular disorders and liver steatosis.

Chlorinated metronidazole as a promising alternative for treating trichomoniasis.

Trichomoniasis is the most common non-viral, sexually transmitted infection affecting humans worldwide. The main treatment for trichomoniasis is metronidazole (MTZ). However, adverse effects and reports of resistance have stimulated the development of therapeutic alternatives. The ease of manipulation of the side chains of MTZ coupled with its safety makes this molecule attractive for the development of new drugs. In this context, we evaluated the activity of the chlorinated MTZ derivative, MTZ-Cl, on sensitive and resistant strains of Trichomonas vaginalis. MTZ-Cl presented a remarkable activity against both sensitive and resistant strains. In vitro and in vivo toxicity assays indicated that the new molecule is safe for future clinical trials. Furthermore, we noticed different rates of free radical production between the sensitive and resistant strains. MTZ-Cl induced a higher release of nitric oxide (NO, ~ 9000a.u.) by both sensitive and resistant strains. However, the sensitive strain produced a greater amount of H2O2 (~ 1,800,000a.u.) and superoxide radicals (~ 350,000a.u.) in the presence of MTZ. In the resistant strain, production of these radicals was more prominent when MTZ-Cl was used. Collectively, these results suggest that NO is an important molecule in the trichomonacidal activity against resistant and sensitive strains, suggesting an alternative pathway for MTZ-Cl activation. We highlight the high trichomonacidal potential of MTZ-Cl, improving the effectiveness of treatment and reducing side effects. In addition, MTZ-Cl is derived from a well-established drug on the world market that presents low toxicity to human cells, suggesting its safety to proceed with future clinical trials.

Oral Microbiota Transplant: A Potential New Therapy for Oral Diseases

Dental caries and periodontitis are amongst the most common diseases affecting humans worldwide. There is an evolving trend for dental and medical research to share knowledge on the etiology and promising therapies for human diseases. Inspired by the success of fecal microbiota transplant to manage gastro-intestinal disordes, oral microbiome transplant has been proposed but not yet tested in humans. This article critically reviews the potential of oral microbiome transplant for managing oral diseases.

Metformin and ascorbic acid combination therapy ameliorates type 2 diabetes mellitus and comorbid depression in rats

Diabetes mellitus and depression are the common comorbid disorders affecting humans worldwide. There is an unmet need to develop therapeutic strategies to treat both diabetes mellitus and comorbid depression. The present study evaluated the effectiveness of metformin and ascorbic acid against type 2 diabetes mellitus and comorbid depression in rats. Four groups of diabetic rats were orally administered with vehicle (1mL/kg), metformin (25mg/kg), ascorbic acid (25mg/kg), or combination of metformin (25mg/kg) and ascorbic acid (25mg/kg) for 11 consecutive days. Diabetes was induced by single-dose administration of streptozotocin (65mg/kg, i.p.) with nicotinamide (120mg/kg, i.p.). Comorbid depression was induced by five inescapable foot-shocks (2mA, 2ms duration) at 10s intervals on days 1, 5, 7, and 10. One group of healthy rats received only vehicles to serve as nondiabetic control group. On day 11, animals were sacrificed, and blood and brain samples were collected from each rat following forced swim test. Plasma glucose, insulin, and corticosterone levels were estimated in plasma. The levels of monoamines, proinflammatory cytokines, and oxidative stress were measured in prefrontal cortex. The combination therapy significantly reduced immobility period, glucose, and corticosterone levels relative to diabetes with comorbid depression group. Furthermore, the combination therapy increased the levels of insulin and monoamines, and caused a significant reductions in oxidative stress and proinflammatory cytokines. In conclusion, the present study revealed that metformin and ascorbic acid combination therapy could be a potential strategy to treat type 2 diabetes mellitus and comorbid depression.