Exposure to toxicologically relevant atrazine concentrations impair the glycolytic function of mouse Sertoli cells through the downregulation of lactate dehydrogenase.

Atrazine (ATZ), a widely used herbicide with potent endocrine-disrupting properties, has been implicated in hormonal disturbances and fertility issues. Sertoli cells (SCs) play a crucial role in providing mechanical and nutritional support of spermatogenesis. Herein, we aimed to study the effects of environmentally relevant ATZ concentrations on the nutritional support of spermatogenesis provided by SCs. For that, mouse SCs (TM4) were exposed to increasing ATZ concentrations (in µg/L: 0.3, 3, 30, 300, or 3000). After 24 h, cellular proliferation and metabolic activity were assessed. Mitochondrial activity and endogenous reactive oxygen species (ROS) production were evaluated using JC-1 and CM-H2DCFDA probes, respectively. We also analyzed protein levels of lactate dehydrogenase (LDH) using Western Blot and live cells glycolytic function through Seahorse XF Glycolysis Stress Test Kit. ATZ exposure decreased the activity of oxidoreductases in SCs, suggesting a decreased metabolic activity. Although ATZ is reported to induce oxidative stress, we did not observe alterations in mitochondrial membrane potential and ROS production across all tested concentrations. When we evaluated the glycolytic function of SCs, we observed that ATZ significantly impaired glycolysis and the glycolytic capacity at all tested concentrations. These results were supported by the decreased expression of LDH in SCs. Overall, our findings suggest that ATZ impairs the glycolytic function of SCs through LDH downregulation. Since lactate is the preferential energetic substrate for germ cells, exposure to ATZ may detrimentally impact the nutritional support crucial for spermatogenesis, hinting for a relationship between ATZ exposure and male infertility.

The infection of Cysticercus fasciolaris in natural rats (Rattus species) residing in human residence areas, Nakhon Si Thammarat, Thailand.

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.

Inter-rater and test-retest reliabilities of lumbar stiffness measurement in the postero-anterior direction using a portable algometer and the Kinovea program.

Background: Back pain negatively impacts a person's quality of life and can cause major disability or even death. The measurement of spinal stiffness can be utilized as a promising tool to guide therapeutic decisions regarding physical therapy that result in effective back pain management. This study aimed to determine the reliability of instrumented postero-anterior (PA) stiffness assessment of the lumbar spine in asymptomatic participants by novice assessors using a portable algometer and the Kinovea program. Methods: Thirty asymptomatic participants aged 18-25 years were enrolled in this study. Two novice assessors examined the participants for lumbar spinal stiffness at L1-L5 for two consecutive days. The algometer was applied to measure the PA force that applied to each lumbar. The stiffness assessment of each lumbar region was recorded as a video. The 600 data sets of assessment videos were imported into the Kinovea program to perform displacement measurements of each lumbar level. Spinal displacement values at 15 N were defined by graph plotting between force and displacement. The spinal stiffness values were defined by slope calculation. Both variables were analyzed for inter-rater and test-retest reliabilities using intra-class correlation coefficients (ICCs) and standard error of measurement (SEM). Bland-Altman analysis was applied to assess the inter-rater and test-retest systematical bias and limits of agreement of measuring displacement and stiffness. Results: The inter-rater reliability of measuring the displacement and the stiffness of L1-L5 was moderate to good (displacement ICCs: 0.67-0.83, stiffness ICCs: 0.60-0.83). The test-retest reliability of measuring the displacement and stiffness of L1-L5 were moderate to good, ICCs: 0.57-0.86 and ICCs: 0.51-0.88, respectively. The inter-rater analysis's Bland-Altman plot showed that the systematic bias was 0.83 when measuring displacement and 0.20 when measuring stiffness and the bias of both parameters were in both directions. While the test-retest systematically biased measurements of displacement and stiffness were -0.26 mm and 0.22 N/mm, respectively, and the bias of both parameters were in both directions. Conclusions: The moderate-to-good inter-rater and test-retest reliabilities of the portable instrumented spinal stiffness assessment using a digital algometer and the Kinovea program by novice assessors were demonstrated in this study. Bland-Altman analysis showed that measuring stiffness was more stable and had less systematic bias than measuring displacement. To figure out how reliable the device is in general, more comprehensive studies should be comparatively conducted in the future on subgroups of patients with normal vertebra, hypomobile or hypermobile conditions.

Systematic review and meta-analysis of the global prevalence of sexually transmitted infections in people living with HIV and associated risk factors.

People living with HIV (PLWH) constitute a vulnerable population for acquiring additional sexually transmitted infections (STIs). This study was conducted to provide a summary of the evidence on the global prevalence of STIs in PLWH with an emphasis on infectious agents, diagnostic methods, and related risk factors. PubMed, Scopus, and Web of Science were systematically searched to include records published from January 01, 1990, to January 31, 2022, and the Google Scholar search engine was used to check the search strategy. In total, 132 eligible studies reporting STIs in PLWH were included, enrolling subjects from 35 countries across five continents. The pooled proportion of STIs was estimated to be 30.23% (95% CI, 26.1-34.45%) in PLWH and 20.01% (95% CI, 17.17-23.01%) in HIV-negative patients. Our meta-analysis indicated that in PLWH, the pooled OR of STIs compared to HIV-negatives was 1.77 (95% CI: 1.58-1.98) (p < 0.0001). The pooled OR of STIs by viral infectious agents was highest in PLWH (52.19% [95% CI: 43.88-60.43]) compared with fungal (22.19% [95% CI: 15.64-29.53]), bacterial (19.07% [95% CI: 13.59-26.63]), and parasitic (14.05% [95% CI: 11.88-16.38]) infections. Our findings show that there is a rather significant frequency of STIs among PLWH. This study highlights the need for new programs for the detection, treatment, and prevention of STIs in this at-risk population.

Induction of TLR5, IRAK1, and NF-κB expression by Trichomonas vaginalis in cervical cancer cell (HeLa) and normal human vaginal epithelial cell (HVECs) lines.

INTRODUCTION: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. METHODOLOGY: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using ß-actin as a housekeeping control. RESULTS: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). CONCLUSIONS: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways.

A Comprehensive Review of the Impact of Chromium Picolinate on Testicular Steroidogenesis and Antioxidant Balance.

Low testosterone (T) levels are a major cause of male infertility, as this hormone is crucial for several processes throughout the entire male reproductive tract. Leydig cells (LC) produce T through testicular steroidogenesis. Disrupted LC function can hinder steroid production and fertility. Among the factors that affect steroidogenesis, endocrine-disrupting chemicals (EDCs) raise concerns, as they disturb hormonal signaling. Chromium is classified as an EDC, and its main forms are hexavalent (Cr(VI)) and trivalent chromium (Cr(III)). While Cr(III) is controversially regarded as an essential metal, its compound Cr(III) picolinate (CrPic3) is used as a nutritional supplement due to its antidiabetic and antioxidant properties. This review aims to identify the possible effects of CrPic3 on testicular steroidogenesis and thus, on male fertility. The detriments caused by CrPic3 in LC include the inhibition of enzymes involved in steroidogenesis, and, as in other cells, the induction of mutagenesis and apoptosis. Remarkably, CrPic3 impacts male fertility through the alteration of reactive oxygen species (ROS), T levels, and sperm parameters (sperm motility and abnormal sperm count). However, gaps and inconsistencies exist in the literature concerning its effects on male fertility. Thus, further research is imperative to comprehend the underlying mechanisms of CrPic3 in the physiological processes relevant to male fertility, ensuring the supplement's safety for use by men.

Microscopic and Molecular Identification of Cyclospora cayetanensis and Cystoisospora belli in HIV-Infected People in Tabriz, Northwest of Iran.

Opportunistic pathogens such as Cryptosporidium, Cystoisospora belli, and Cyclospora cayetanensis cause various gastrointestinal and non-digestive disorders in people with HIV/AIDS. These symptoms are especially severe in HIV-infected people who have a CD4+ count of less than 200 cells/mL. This study aimed to determine the prevalence of C. belli and C. cayetanensis infections among people living with HIV in Tabriz, northwest of Iran. This descriptive study was performed on 137 people with HIV who had been referred to behavioral disease counseling centers in Tabriz. Then, after receiving written consent, fecal samples were collected and evaluated for the detection of parasitic infections using direct methods and modified acid fast staining, as well as polymerase chain reaction (PCR).From the 137 fecal samples collected (98 males and 39 females, between 20 and 40 years old), 1.5% were positive for C. cayetanensis and 2.9% were positive for C. belli. Due to the prevalence of C. cayetanensis and C. belli in people with HIV in Tabriz, essential measures, including personal hygiene training for infection control and prevention, seem necessary.

Analysis of Biochemical and Antimicrobial Properties of Bioactive Molecules of Argemone mexicana.

This study identified phytochemicals in Argemone mexicana (A. mexicana) extracts that are responsible for its medicinal properties, and the best solvent for their extraction. The extracts of the stem, leaves, flowers, and fruits of A. mexicana were prepared at low (corresponding to room temperature) and high temperatures (corresponding to the boiling points) in various solvents, viz., hexane, ethyl acetate, methanol, and H2O. The UV-visible absorption spectra of various phytoconstituents in the isolated extracts were determined through spectrophotometry. Qualitative tests for the screening of phytoconstituents in the extracts were performed to identify various phytochemicals. We identified the presence of terpenoids, alkaloids, cardiac glycosides, and carbohydrates in the plant extracts. The antioxidant and anti-human immunodeficiency virus type 1 reverse transcriptase (anti-HIV-1RT) potential, as well as the antibacterial activity of various A. mexicana extracts were determined. These extracts showed strong antioxidant activities. The extracts exhibited antimicrobial activities against Salmonella typhi, Staphylococcus epidermis, Citrobacter, Neisseria gonorrhoeae, and Shigella flexineri. These extracts significantly inhibited HIV-1 reverse transcriptase activity. The aqueous leaf extract prepared at a temperature equivalent to the boiling point, i.e., 100 °C, was identified to be the most active against pathogenic bacteria and HIV-1 RT.

Trypanosoma lewisi in blood of Rattus rattus complex residing in human settlements, Nakhon Si Thammarat, Thailand: Microscopic and molecular investigations.

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.

Elucidation of the Anticancer Mechanism of Durian Fruit (Durio zibethinus) Pulp Extract in Human Leukemia (HL-60) Cancer Cells.

Durian (Durio zibethinus L.) grows widely in Southeast Asia. The pulp of the durian fruit contains carbohydrates, proteins, lipids, fibers, various vitamins, minerals, and fatty acids. This study was carried out to elucidate the anticancer mechanism of action of the methanolic extract of the fruit of Durio zibethinus (D. zibethinus) on human leukemia (HL-60) cells. The methanolic extract of D. zibethinus fruits exhibited its anticancer effect on HL-60 cells by inducing DNA damage and apoptosis. The DNA damage was confirmed by comet and DNA fragmentation assays. The methanolic extract of D. zibethinus fruits has been shown to cause cell cycle arrest in HL-60 cells during the S phase and G2/M phase. Additionally, the methanolic extract caused induction of the apoptotic pathway in the HL-60 cell line. This was confirmed by increased expression in pro-apoptotic proteins, viz., Bax protein expression, and a substantial reduction (p < 0.001) in anti-apoptotic proteins, viz., Bcl-2 and Bcl-xL expressions. Therefore, this study confirms that the methanolic extract of D. zibethinus exerts its anticancer effects on the HL-60 cell line, causing cell cycle arrest and induction of apoptosis by an intrinsic mechanism.

Are Fermented Foods Effective against Inflammatory Diseases?

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.

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices.

Type 1 diabetes mellitus (T1DM) is the most common autoimmune chronic disease in young patients. It is caused by the destruction of pancreatic endocrine ß-cells that produce insulin in specific areas of the pancreas, known as islets of Langerhans. As a result, the body becomes insulin deficient and hyperglycemic. Complications associated with diabetes are life-threatening and the current standard of care for T1DM consists still of insulin injections. Lifesaving, exogenous insulin replacement is a chronic and costly burden of care for diabetic patients. Alternative therapeutic options have been the focus in these fields. Advances in molecular biology technologies and in microfabrication have enabled promising new therapeutic options. For example, islet transplantation has emerged as an effective treatment to restore the normal regulation of blood glucose in patients with T1DM. However, this technique has been hampered by obstacles, such as limited islet availability, extensive islet apoptosis, and poor islet vascular engraftment. Many of these unsolved issues need to be addressed before a potential cure for T1DM can be a possibility. New technologies like organ-on-a-chip platforms (OoC), multiplexed assessment tools and emergent stem cell approaches promise to enhance therapeutic outcomes. This review will introduce the disorder of type 1 diabetes mellitus, an overview of advances and challenges in the areas of microfluidic devices, monitoring tools, and prominent use of stem cells, and how they can be linked together to create a viable model for the T1DM treatment. Microfluidic devices like OoC platforms can establish a crucial platform for pathophysiological and pharmacological studies as they recreate the pancreatic environment. Stem cell use opens the possibility to hypothetically generate a limitless number of functional pancreatic cells. Additionally, the integration of stem cells into OoC models may allow personalized or patient-specific therapies.

Knema retusa is antibacterial and antibiofilm against antibiotic resistant Staphylococcus aureus and S. haemolyticus isolated in bovine mastitis.

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.

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

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.

In vitro efficacy of albendazole-loaded ß-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto.

BACKGROUND: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. METHODS: We evaluated the apoptotic effects of ABZ-loaded ß-cyclodextrin (ABZ-ß-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-ß-CD groups. To assess the treatment efficacy of ABZ-ß-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. RESULTS: A significant scolicidal activity of ABZ was observed only at a concentration of 800 µg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 µg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 µg/mL ABZ-ß-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 µg/mL ABZ-ß-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 µg/mL ABZ-ß-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. CONCLUSIONS: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 µg/mL ABZ-ß-CD compared to ABZ alone. This provides new insights into the use of nanostructured ß-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.

Synthesis of M-Ag3PO4, (M = Se, Ag, Ta) Nanoparticles and Their Antibacterial and Cytotoxicity Study.

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.

Antibacterial and Antifungal Alkaloids from Asian Angiosperms: Distribution, Mechanisms of Action, Structure-Activity, and Clinical Potentials.

The emergence of multidrug-resistant bacteria and fungi requires the development of antibiotics and antifungal agents. This review identified natural products isolated from Asian angiosperms with antibacterial and/or antifungal activities and analyzed their distribution, molecular weights, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1979 to 2022. One hundred and forty-one antibacterial and/or antifungal alkaloids were identified during this period, mainly from basal angiosperms. The most active alkaloids are mainly planar, amphiphilic, with a molecular mass between 200 and 400 g/mol, and a polar surface area of about 50 Å2, and target DNA and/or topoisomerase as well as the cytoplasmic membrane. 8-Acetylnorchelerythrine, cryptolepine, 8-hydroxydihydrochelerythrine, 6-methoxydihydrosanguinarine, 2'-nortiliacorinine, pendulamine A and B, rhetsisine, sampangine, tiliacorine, tryptanthrin, tylophorinine, vallesamine, and viroallosecurinine yielded MIC ≤ 1 µg/mL and are candidates for the development of lead molecules.

Virulence Characteristics and Emerging Therapies for Biofilm-Forming Acinetobacter baumannii: A Review.

Acinetobacter species is one of the most prevailing nosocomial pathogens with a potent ability to develop antimicrobial resistance. It commonly causes infections where there is a prolonged utilization of medical devices such as CSF shunts, catheters, endotracheal tubes, and similar. There are several strains of Acinetobacter (A) species (spp), among which the majority are pathogenic to humans, but A. baumannii are entirely resistant to several clinically available antibiotics. The crucial mechanism that renders them a multidrug-resistant strain is their potent ability to synthesize biofilms. Biofilms provide ample opportunity for the microorganisms to withstand the harsh environment and further cause chronic infections. Several studies have enumerated multiple physiological and virulence factors responsible for the production and maintenance of biofilms. To further enhance our understanding of this pathogen, in this review, we discuss its taxonomy, pathogenesis, current treatment options, global resistance rates, mechanisms of its resistance against various groups of antimicrobials, and future therapeutics.

Carbamate Pesticides: Shedding Light on Their Impact on the Male Reproductive System.

Carbamates are widely used and known around the world as pesticides in spite of also having medical applications. This class of chemicals is classified as acetylcholinesterase inhibitors, blocking acetylcholine hydrolyzation in a reversible manner. Their lack of species selectivity and their reported high toxicity can induce, upon exposure, adverse outcomes in male fertility that may lead to infertility. In addition, they are also considered endocrine-disrupting chemicals and can interfere with the hypothalamic-pituitary-testicular axis, essential for the normal function of the male reproductive system, thus being able to provoke male reproductive dysfunctions. Although the molecular mechanisms are not fully understood, various signaling pathways, such as those mediated by acetylcholine or kisspeptin, are affected by exposure to carbamates, thus compromising steroidogenesis and spermatogenesis. Over the last decades, several studies, both in vitro and in vivo, have reported a myriad of negative effects of carbamates on the male reproductive system. In this review, an up-to-date overview of the impact of carbamates on the male reproductive system is discussed, with an emphasis on the role of these compounds on acetylcholine regulation and the male endocrine system.

Solanaceae Family Phytochemicals as Inhibitors of 3C-Like Protease of SARS-CoV-2: An In Silico Analysis.

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.