Global Dilemma and Needs Assessment Toward Achieving Sustainable Development Goals in Controlling Leishmaniasis.

Leishmaniasis is a disease of poverty that imposes a devastating medical, social, and economic burden on over 1 billion people nationwide. To date, no in-depth study to analyze the major global challenges and needs assessment has been carried out. This investigation aimed to explore a comprehensive narrative review of leishmaniasis's main challenges and initially highlight obstacles that might impede the implementation of control measures. Also, we propose a specific list of priorities for needs assessment. The presence of socioeconomic factors, multiple clinical and epidemiological forms, various Leishmania species, the complexity of the life cycle, the absence of effective drugs and vaccines, and the lack of efficient vector and reservoir control make this organism unique and sophisticated in playing a tangled role to react tricky with its surrounding environments, despite extensive efforts and implementation of all-inclusive former control measures. These facts indicate that the previous strategic plans, financial support, and basic infrastructures connected to leishmaniasis surveillance are still insufficient. Strengthening the leishmaniasis framework in a context of accelerated programmatic action and intensification of cross-cutting activities along with other neglected tropical diseases (NTDs) is confidently expected to result in greater effectiveness, cost-benefit, and fruitful management. Sensitive diagnostics, effective therapeutics, and efficacious vaccines are vital to accelerating advancement toward elimination, and reducing morbidity/mortality and program costs. Collective actions devoted by all sectors and policy-makers can hopefully overcome technical and operational barriers to guarantee that effective and coordinated implementation plans are sustained to meet the road map for NTDs 2021- 2030 goals.

Cutaneous Leishmaniasis Hampers COVID-19: A Controlled Cross-Sectional Study in High-Burden Endemic Areas of Iran.

INTRODUCTION: Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case-control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history. METHODS: This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth's bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups. RESULTS: The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06-0.20 and P < 0.001) and severity of COVID-19 in previous cases with CL scars were significantly diminished than that in the control group (credible interval - 2.57, - 1.62). CONCLUSIONS: The results represented a durable negative relationship between cured CL and COVID-19 incidence and severity. Additional studies seem necessary and should be designed to further validate the true impact and underlying mechanistic action of CL on COVID-19.

Comparison of cytotoxicity of Miltefosine and its niosomal form on chick embryo model.

Various drugs have been used for the treatment of leishmaniasis, but they often have adverse effects on the body's organs. In this study, we aimed to explore the effects of one type of drug, Miltefosine (MIL), and its analogue or modifier, liposomal Miltefosine (NMIL), on several fetal organs using both in silico analysis and practical tests on chicken embryos. Our in silico approach involved predicting the affinities of MIL and NMIL to critical proteins involved in leishmaniasis, including Vascular Endothelial Growth Factor A (VEGF-A), the Kinase insert domain receptor (KDR1), and apoptotic-regulator proteins (Bcl-2-associate). We then validated and supported these predictions through in vivo investigations, analyzing gene expression and pathological changes in angiogenesis and apoptotic mediators in MIL- and NMIL-treated chicken embryos. The results showed that NMIL had a more effective action towards VEGF-A and KDR1 in leishmaniasis, making it a better candidate for potential operative treatment during pregnancy than MIL alone. In vivo, studies also showed that chicken embryos under MIL treatment displayed less vascular mass and more degenerative and apoptotic changes than those treated with NMIL. These results suggest that NMIL could be a better treatment option for leishmaniasis during pregnancy.

Aberrant expression of SOCS impairs the anti-leishmanial immune response.

Establishing a balance between Th1 and Th2 subsets and M1- and M2-type macrophages is essential for the control of Leishmania infection. The suppressors of cytokine secretion (SOCS) proteins, particularly SOCS1 and SOCS3, play a significant role in regulating cytokine-triggered signaling pathways, thereby impacting the macrophage-and effector T-cell mediated antileishmanial immune response. In addition to the pro-inflammatory cytokines, Leishmania-derived lipophosphoglycan (LPG) and CpG-DNA interact with TLR2 and TLR9 to trigger SOCS expression. The aberrant levels of SOCS1 and SOCS3 expression in Leishmania-infected macrophages impair macrophage-T-cell interaction perturbing the balance in macrophage subsets polarization. This hinders macrophage apoptosis and macrophage-mediated leishmanicidal activity, both support the establishment of infection and parasite replication. Furthermore, aberrant SOCS3 levels in T-cells disrupt Th1 differentiation and aid in parasite replication, lesion development, and pathological immune responses. Strategically, selective modulation of SOCS expression and function in immune effector cells may reduce parasite survival and prevent disease progression.

A prospective longitudinal study on the elimination trend of rural cutaneous leishmaniasis in southeastern Iran: Climate change, population displacement, and agricultural transition from 1991 to 2021.

Leishmaniasis is a complex disease. Any change in weather conditions affects the humans' social and agricultural expansion and, consequently, the parasite's life cycle in terms of ecology, biodiversity, social stigma, and exclusion. This population-based prospective longitudinal investigation was conducted between 1991 and 2021 in a well-defined CL (cutaneous leishmaniasis) focus in Bam County, southeastern Iran. A robust health clinic and health surveillance system were responsible for the ongoing systematic documentation, detection, identification, and management of CL cases. The exponential smoothing method via the state space model was used in the univariate time series. The TTR, smooth, and forecast packages were used in R software. Landsat satellite images from 1991, 2001, 2011, and 2021 were employed in the physical development. During this period, the temperature increased while the rainfall and humidity decreased. The findings showed a downward trend in the standardized drought index. Also, the results showed that climate warming and ecological changes profoundly affected the area's agricultural patterns and topographical features. Furthermore, the last three decades witnessed an elimination trend for zoonotic CL (ZCL) and the predominance of anthroponotic CL (ACL). The present findings showed that the critical factors in the predominance of ACL and elimination of ZCL were rising temperature, drought, migration, unplanned urbanization, earthquake, and agrarian reform. The wall-enclosed palm tree gardens excluded the primary ZCL reservoir host. They controlled the disease while providing suitable conditions for the emergence/re-emergence of ACL in the newly established settlements and the unplanned ecozone. Therefore, robust health infrastructures, sustained financial support, and evidence-based research studies are crucial to facilitating the necessary surveillance, monitoring, and evaluation to control and eliminate the disease.

Geographical and climatic risk factors of cutaneous leishmaniasis in the hyper-endemic focus of Bam County in southeast Iran.

Introduction: Cutaneous leishmaniasis (CL) is a prevalent debilitating disease in many countries, particularly in Iran, the Middle East, North Africa, and South America. Bam County is the most important highly endemic focus of anthropometric CL in Iran and has been under consideration by WHO. This study investigated the environmental and geographic factors affecting the occurrence and distribution of CL in this focus. Methods: Demographic data and the home addresses of CL patients diagnosed from 2015 to 2020 were retrieved from the Leishmaniasis Center of Bam in southeast Iran. The effects of mean annual rainfall (MAR), mean annual humidity (MAH), mean annual temperature (MAT), maximum annual temperature (MaxMAT), minimum annual temperature (MinMAT), mean annual humidity (MAH), mean annual evaporation (MAE), mean annual frosty days (MAFD), mean annual snowy hours (MASH), elevation, and land cover on the distribution of CL were analyzed using geographical information systems (GIS) and univariate and multivariate regression models. Results: Of 847 patients studied, 50.9% (n = 431) were female and 49.1% (n = 416) were male. The age classes 0-10 (n = 246) and 11-20 (n = 145) showed the highest frequency of patients, respectively. Leishmaniasis patients were reported from 66 villages/cities (11.8%) out of 561 residential areas in Bam County. Univariate analysis showed that urban settings (OR = 21.66), agriculture (OR = 5.73), orchards (OR = 5), salty land (OR = 1.05), and temperatures (OR = 2.37, 2.79 and 3.47) had positive effects on CL occurrence (p < 0.05), while altitude, precipitation, humidity, evaporation, and the number of frozen days had negative effects. Multivariate analysis identified urban settings (OR = 13.6), orchards (OR = 6.29), agriculture (OR = 5.82), and minimum temperature (OR = 2.38) as the most significant determinants of CL occurrence in this region. Conclusion: Environmental and ecological factors play an important role in the distribution of CL in Bam County. The high-risk zones for CL are cities/large villages, agricultural and orchard areas in lower altitudes and with warmer climates and lower rainfall and humidity. This model can guide researchers and health managers to properly conduct CL control programs and allocate budgets.

Visceral Leishmaniasis in Iran: An Update on Epidemiological Features from 2013 to 2022.

Background: Visceral leishmaniasis (VL) is one of the most important neglected tropical diseases. The zoonotic form of VL is endemic in some areas of Iran. We aimed to determine the status of VL identified in humans and canines in different parts of Iran from 2013 to 2022. Method: A national representative cross-sectional study was conducted in 10 provinces of Iran, including the national leishmaniasis reference lab. We employed the direct agglutination test (DAT) as a reliable serological method to detect anti-Leishmania infantum antibodies in humans and animal reservoir hosts. Additionally, a narrative literature review was conducted to identify relevant studies on VL seroprevalence in Iran from 2013 to 2023. Results: The results of 21281 human and 5610 canine serum samples from 2013 to 2022 are reported. Altogether, 448 (2.1%, 95%CI: 2.0-2.3) human serum samples showed anti-L. infantum antibody levels of ≥1:3200. Of these samples, 13716 (64.5%) were collected actively, which showed a seroprevalence of 0.6% (95% CI: 0.5-0.8) and 7565 (35.5%) were collected passively, which showed a seroprevalence of 4.8% (95%CI: 4.3-5.3). Overall, 1035 (20.1%, 95%CI: 19.0-21.2) of 5160 domestic dogs (Canis familiaris) samples showed anti-L. infantum antibody levels of ≥1:320. Northwest (2.8%) and northeast (0.96%) regions had the highest human VL seroprevalence, while northwest (21.5%) and south (14.4%) regions had the highest canine VL seroprevalence. Conclusion: Zoonotic VL, an endemic parasitic disease, is still present in several different distinct areas across Iran. While human VL cases have shown a declining trend over the last decade, the prevalence of canine VL remains significant.

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation.

The advancements in nanoscience have brought attention to the potential of utilizing nanoparticles as carriers for oral insulin administration. This study aims to investigate the effectiveness of synthesized polymeric mesoporous silica nanoparticles (MSN) as carriers for oral insulin and their interactions with insulin and IR through in-silico docking. Diabetic rats were treated with various MSN samples, including pure MSN, Amin-grafted MSN/PEG/Insulin (AMPI), Al-grafted MSN/PEG/Insulin (AlMPI), Zinc-grafted MSN/PEG/Insulin (ZNPI), and Co-grafted MSN/PEG/Insulin (CMPI). The nanocomposites were synthesized using a hybrid organic-inorganic method involving MSNs, graphene oxide, and insulin. Characterization of the nanocomposites was conducted using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). In vivo tests included the examination of blood glucose levels and histopathological parameters of the liver and pancreas in type 1 diabetic rats. The MSN family demonstrated a significant reduction in blood glucose levels compared to the diabetic control group (p < 0.001). The synthesized nanocomposites exhibited safety, non-toxicity, fast operation, self-repairing pancreas, cost-effectiveness, and high efficiency in the oral insulin delivery system. In the in-silico study, Zn-grafted MSN, Co-grafted MSN, and Al-grafted MSN were selected. Docking results revealed strong interactions between MSN compounds and insulin and IR, characterized by the formation of hydrogen bonds and high binding energy. Notably, Co-grafted MSN showed the highest docking scores of -308.171 kcal/mol and -337.608 kcal/mol to insulin and IR, respectively. These findings demonstrate the potential of polymeric MSN as effective carriers for oral insulin, offering promising prospects for diabetes treatment.

In silico and in vitro potentials of crocin and amphotericin B on Leishmania major: Multiple synergistic mechanisms of actions.

A significant barrier to optimal antileishmanial treatment is low efficacy and the emergence of drug resistance. Multiple approaches were used to monitor and assess crocin (a central component of saffron) mixed with amphotericin B (AmpB) potential in silico and in vitro consequences. The binding behavior of crocin and iNOS was the purpose of molecular docking. The results showed that crocin coupled with AmpB demonstrated a safe combination, extremely antileishmanial, suppressed Leishmania arginase absorption, and increased parasite death. This natural flower component is a robust antioxidant, significantly promoting the expression of the Th1-connected cytokines (IL12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (Elk-1, c-Fos, and STAT-1). In comparison, the expression of the Th2-associated phenotypes (IL-10, IL-4, and TGF-ß) was significantly reduced. The leishmanicidal effect of this combination was also mediated through programmed cell death (PCD), as confirmed by the manifestation of phosphatidylserine and cell cycle detention at the sub-GO/G1 phase. In conclusion, crocin with AmpB synergistically exerted in vitro antileishmanial action, generated nitric oxide and reactive oxygen species, modulated Th1, and Th2 phenotypes and transfer factors, enhanced PCD profile and arrested the cell cycle of Leishmania major promastigotes. The main action of crocin and AmpB involved wide-ranging mechanistic insights for conducting other clinical settings as promising drug candidates for cutaneous leishmaniasis. Therefore, this combination could be esteemed as a basis for a potential bioactive component and a logical source for leishmanicidal drug development against CL in future advanced clinical settings.

Antileishmanial potentials of azacitidine and along with meglumine antimoniate on Leishmania major: In silico prediction and in vitro analysis.

This study aimed to investigate the in vitro and in silico antileishmanial activity of azacitidine (AZA) on Leishmania major promastigotes and amastigotes. The in silico method was used to evaluate the possibility of the interaction of AZA into the binding pocket of inducible nitric oxide synthase (iNOS), a leading defensive oxidative metabolite. Following that, in vitro anti-promastigote, and anti-amastigote activity of AZA was determined using an MTT assay and a macrophage model, respectively. Cytotoxic effects of AZA and meglumine antimoniate (MA) were also assessed by MTT assay on murine macrophages. All experiments were performed in triplicate. The results showed that AZA interacted with Ser133, Gln134, and Lys13 amino acids of iNOS, and the molecular docking score was obtained at -241.053 kcal/mol. AZA in combination with MA significantly (P<0.001) inhibited the growth rate of nonclinical promastigote (IC50 247.6±7.3 µM) and 8.5-fold higher of clinical intramacrophage amastigote stage (29.8±5.3 µM), compared to the untreated group. A significant upsurge of Th1 subsets and transcription genes and a meaningful decline in Th2 cytokines subclasses at the equivalent concentrations of AZA and MA was observed (P<0.001). The apoptosis effect of AZA along with MA was significantly induced on L. major in a dose-dependent manner (P<0.001). The present study demonstrated that AZA possesses antileishmanial activity in in vitro and in silico models. However, AZA combined with MA was more effective than AZA alone in inhibiting the growth rate of promastigotes and amastigotes of L. major. This study indicates that AZA in combination with MA demonstrated a potent antileishmanial mechanism, promoting immune response and enhancing an immunomodulatory role toward the Th1 pathway. This experimental study is a basic study for applying more knowledge about the mechanisms of AZA along with MA in animal models in the future.

Monitoring of airborne fungi during the second wave of COVID-19 in selected wards of the referral university hospital in southeastern Iran.

Microbiological monitoring of the air hospital is essential for prevention and control, due to the possible airborne route of infection transmission, especially in high-risk wards. This study aimed to monitor the airborne fungi during the second wave of the COVID-19 pandemic in selected wards of the biggest university educational hospital in Kerman, southeastern Iran. This study was conducted in 11 different wards, separated into the patient room and nursing station, of the Afzalipour hospital from May to August 2021. Fungal isolates were characterized to the species level by conventional and sequencing methods. Out of 93 obtained fungal colonies, 70 (75.3%) isolates were filamentous and 23 (24.7%) isolates were yeast. Aspergillus species were the predominant fungal isolates among the filamentous colonies (n=19; 27.1%), and Naganishia albida (formerly Cryptococcus albidus) was identified as the most common yeast isolate (n=13/23; 56.8%). The infectious ward was the most contaminated unit (n=19/93), while the least contaminated units were the neonatal intensive care unit (n=3/93), and oncology (n=3/93). The statistical findings displayed that the number of fungal isolates in patients' rooms is significantly higher than in nurses' stations (p-value=0.013). Our study demonstrated the presence of diverse fungal species in all wards of the hospital. Considering the presence of airborne fungi in hospitals and related public health problems is one of the critical issues for health systems management. In this regard, efficient monitoring of airborne fungi might play an influential role in hospital infection control and surveillance, particularly in high-risk hospitalization patients in critical wards.

Antileishmanial effects and drugability characteristics of a heterocyclic copper complex: An in silico, in vitro and molecular study.

Leishmaniasis caused by the protozoan Leishmania presents a severe illness, principally in tropical and subtropical areas. Antileishmanial metal complexes, like Glucantime®ï¸ with proven activity, are routinely studied to probe their potency. We investigated the effects of a Cu (II) homoleptic complex coordinated by two dimethyl-bipyridine ligands against Leishmania major stages in silico and in vitro. The affinity of this heterocyclic Cu (II) complex (CuDMBP) towards a parasitic metacaspase was studied by molecular docking. Key pharmacokinetic and pharmacodynamic properties of the complex were predicted using three web-based tools. CuDMBP was tested for in vitro antileishmanial activities using MTT assay, model murine macrophages, flow cytometry, and quantitative real-time polymerase chain reaction (qPCR). Molecular docking confirmed the tendency between the target macromolecule and the complex. ADMET evaluations highlighted CuDMBP's key pharmacological features, including P-glycoprotein-associated GI absorption and lack of trans-BBB permeability. MTT showed significant inhibitory effects against promastigotes. CuDMBP significantly increased the level of cellular IL-12 expression (p < 0.05), while the upregulation observed in the expression of iNOS was considered not significant (p > 0.05). It decreased the expression of IL-10 significantly (p < 0.05). Findings demonstrated that CuDMBP deserves to be introduced as a leishmanicidal candidate provided further studies are carried out.

Cutaneous leishmaniasis situation analysis in the Islamic Republic of Iran in preparation for an elimination plan.

Iran has invariably been under the growing public health threat of cutaneous leishmaniasis (CL), a significant barrier to local development that hinders the prevention and control efforts toward eliminating the disease. So far, no comprehensive and in-depth epidemiological analysis of the CL situation has been carried out nationwide. This study aimed to employ advanced statistical models to analyze the data collected through the Center for Diseases Control and Prevention of Communicable Diseases during 1989-2020. However, we emphasized the current trends, 2013-2020, to study temporal and spatial CL patterns. In the country, the epidemiology of CL is incredibly intricate due to various factors. This fact indicates that the basic infrastructure, the preceding supports, and the implementation plan related to preventive and therapeutic measures need crucial support. The leishmaniasis situation analysis is consistent with desperate requirements for efficient information on the control program in the area. This review provides evidence of temporally regressive and spatially expanding incidence of CL with characteristic geographical patterns and disease hotspots, signifying an urgent need for comprehensive control strategies. This information could be a suitable model and practical experience in the Eastern Mediterranean Region, where over 80% of CL is reported.

Synthesis and physicochemical characterization of Zn-Al layered double hydroxides (LDHs) as a delivery system for amphotericin B: In vitro and in silico antileishmanial study.

Leishmaniasis as a widespread neglected vector-borne protozoan disease is a major public health concern in endemic areas due to 12 million people affected worldwide and 60,000 deaths annually. Several problems and side effects in using current chemotherapies leads to progression of new drug delivery systems against leishmaniasis. For instance, layered double hydroxides (LDHs) so-called anionic clays due to their proper characteristics, have been considered recently. In the present study, LDH nanocarriers were prepared using co-precipitation method. Then, the intercalation reactions with amphotericin B were conducted via indirect ion exchange assay. Finally, after characterization of prepared LDHs, the anti-leishmanial effects of Amp-Zn/Al-LDH nanocomposites against Leishmania major were evaluated using an in vitro and in silico model. According to results, current study demonstrated that Zn/Al-NO3 LDH nanocarriers can be used as a new promising delivery system by intercalating amphotericin B into its interlayer space for leishmaniasis treatment by eliminating the L. major parasites by remarkable immunomodulatory, antioxidant and apoptotic effects.

The potential effect of silver nanoparticles synthesized with Coffea arabica green seeds on Leishmania major proliferation, cytotoxicity activity, and cytokines expression level.

The goal of this study was to analyze the antileishmanial and antibacterial activity of Coffea arabica green seed biosynthesize silver nanoparticles (C. arabica AgNPs), as well as cytotoxicity and cytokine gene expression. UV-vis spectroscopy, FTIR, and FESEM methods used to examine the C. arabica AgNPs. MTT test was used to assess the antileishmanial and cytotoxicity effects. The gene expression level was assessed in NPs-treated J774 cells by qPCR. The synthesized C. arabica AgNPs were in the size range of 20-70 nm, through FESEM pictures. The IC50 values of the NPs were 65. 4 and 47.70 µg/mL against promastigotes and amastigotes of Leishmania major, but these values were 580.1 and 171.1 µg/mL for Glucantime® as the control drug. C. arabica AgNPs represented a significant increase in IL-12P40, as a Th1 cytokine, in comparison to Glucantime® at high concentrations (P < 0.01), whilst IL-10 expression level showed a significant reduction between NPs-treated and Glucantime®-treated macrophages at 250-1000 µg/mL concentrations (P < 0.001). Moreover, the NPs were cytotoxic on cancer cell lines of Hek293, MCF7, and A172 with the CC50 values of 437.2, 116.8, and 72.9 µg/mL, respectively. It showed a significant effect of these NPs against A172 (P < 0.001). Also, the lowest MIC values of the NPs were obtained for Bacillus subtilis and Staphylococcus aureus (204 µg/mL). According to the antileishmanial, anticancer, and antibacterial activity of these NPs, it can considered a bio-agent drug in the future in endemic countries.

The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo.

Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients' health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes. Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone. Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.

Bioinformatics evaluation of anticancer properties of GP63 protein-derived peptides on MMP2 protein of melanoma cancer.

Background: GP63, also known as Leishmanolysin, is a multifunctional virulence factor abundant on the surface of Leishmania spp. small peptides with anticancer capabilities that are selective and toxic to cancer cells are known as anticancer peptides. We aimed to demonstrate the activity of GP63 and its anticancer properties on melanoma using a range of in silico tools and screening methods to identify predicted and designed anticancer peptides. Methods: Various in silico modeling methodologies are used to establish the three-dimensional (3D) structure of GP63. Refinement and re-evaluation of the modeled structures and the built models' quality evaluated using the different docking used to find the interacting amino acids between MMP2 and GP63 and its anticancer peptides. AntiCP2.0 is used for screening anticancer peptides. 2D interaction plots of protein-ligand complexes evaluated by Protein-Ligand Interaction Profiler server. It is for the first time that used anticancer peptides of GP63 and the predicted and designed peptides. Results: We used 3 peptides of GP63 based on the AntiCP 2.0 server with scores of 0.63, 0.53, and 0.49, and common peptides of GP63/MMP2 (continues peptide: mean the completely selected peptide after docking with non-anticancer effect, predicted with 0.58 score and designed peptides with 0.47 and 0.45 scores by AntiCP 2.0 server). Conclusions: The antileishmanial and anticancer peptide research topics exemplify the multidisciplinary nature of peptide research. The advancement of therapeutics targeting cancer and/or Leishmania requires an interconnected research strategy shown in this work.

Poor adherence is a major barrier to the proper treatment of cutaneous leishmaniasis: A case-control field assessment in Iran.

Leishmaniasis is an overlooked, poverty-stricken, and complex disease with growing social and public health problems. In general, leishmaniasis is a curable disease; however, there is an expansion of unresponsive cases to treatment in cutaneous leishmaniasis (CL). One of the effective and ignored determinants in the treatment outcome of CL is poor treatment adherence (PTA). PTA is an overlooked and widespread phenomenon to proper Leishmania treatment. This study aimed to explore the effect of poor adherence in unresponsiveness to treatment in patients with anthroponotic CL (ACL) by comparing conventional statistical modalities and machine learning analyses in Iran. Overall, 190 cases consisting of 50 unresponsive patients (case group), and 140 responsive patients (control group) with ACL were randomly selected. The data collecting form that included 25 queries (Q) was recorded for each case and analyzed by R software and genetic algorithm (GA) approaches. Complex treatment regimens (Q11), cultural and lay views about the disease and therapy (Q8), life stress, hopelessness and negative feelings (Q22), adverse effects of treatment (Q13), and long duration of the lesion (Q12) were the most prevalent significant variables that inhibited effective treatment adherence by the two methods, in decreasing order of significance. In the inherent algorithm approach, similar to the statistical approach, the most significant feature was complex treatment regimens (Q11). Providing essential knowledge about ACL and treatment of patients with chronic diseases and patients with misconceptions about chemical drugs are important issues directly related to the disease's unresponsiveness. Furthermore, early detection of patients to prevent the long duration of the disease and the process of treatment, efforts to minimize side effects of treatment, induction of positive thinking, and giving hope to patients with stress and anxiety by medical staff, and family can help patients adhere to the treatment.

Antileishmanial Effects of Bunium Persicum Crude Extract, Essential Oil, and Cuminaldehyde on Leishmania Major: In Silico and In Vitro Properties.

PURPOSE: Cuminaldehyde (CA), an oxidized aldehyde monoterpene, is a major essential oil component in cumin seeds, which has shown different promising medical effects. In this study, we comprehensively evaluated the antileishmanial potential of Bunium persicum (Boiss) B. Fedtsch (Apiaceae) and one of its main essential oil constituents, CA, focus on the mechanisms of action. METHODS: We used a molecular docking approach to examine the capability of CA for binding to IL-12P40 and TNF-α. The colorimetric assay was performed to assess the effect of B. persicum crude extract, essential oil, and CA, against Leishmania major promastigotes and intracellular amastigotes. The expression of IFN-γ, IL-12P40, TNF-α, and IL-10 genes was detected using quantitative real-time polymerase chain reaction qPCR. RESULTS: Docking analyses in the current study indicated CA binds to IL-12P40 and TNF-α. These products were safe, extremely antileishmanial, and significantly promoted Th1-related cytokines (IFN-γ, IL-12P40, TNF-α), while downregulating the Th2 phenotype (IL-10). CONCLUSION: Cumin essential oil and its major component, CA, possessed powerful antileishmanial activity. The primary mechanism of activity involves an immunomodulatory role toward Th1 cytokine response. Therefore, cumin essential oil and CA deserve further explorations as promising medications for treating leishmaniasis.

Vulvovaginal candidiasis in Iranian women: Molecular identification and antifungal susceptibility pattern.

AIM: Vulvovaginal candidiasis (VVC), is a common fungal infection that remains a global concern. The objectives of this study were molecular identification and assessment of the antifungal susceptibility profile of Candida species, causing VVC in southeast Iran. METHODS: A cross-sectional investigation was carried out on 119 nonpregnant females suspected of VVC between February 2019 and May 2021. Yeast samples were characterized to the species level by conventional and molecular methods. All Candida isolates were examined for in vitro susceptibility profile to six conventional antifungal drugs using Clinical and Laboratory Standards Institute guidelines. RESULTS: Out of 119 subjects, 52 (43.7%) cases were affected by VVC, out of whom 11 (21.15%) cases had recurrent vulvovaginal candidiasis (RVVC). The species distribution was as follows; Candida albicans (n = 21; 40.4%), C. glabrata (n = 11; 21.2%), C. tropicalis (n = 9; 17.3%), C. parapsilosis (n = 5; 9.7%), C. africana (n = 3; 5.7%), C. famata (n = 1; 1.9%), C. lusitaniae (n = 1; 1.9%), and C. dubliniensis (n = 1; 1.9%). The resistance rate of Candida isolates to fluconazole, itraconazole, and voriconazole were 15.38%, 11.5%, and 3.8%, respectively. Resistance to fluconazole was obtained in 46% (5/11) of RVVC cases but only in 7% (3/41) of VVC cases. CONCLUSION: This study demonstrated that the majority of VVC cases were caused by non-albicans Candida species which also were resistant to some antifungal agents. Hence, our findings revealed the importance of conducting periodical epidemiological studies to determine changes in species distribution. Moreover, for effective management of treatment and infection, it is imperative to evaluate the susceptibility profiles of Candida species isolated from VVC patients.