Glioblastoma is the most common and aggressive primary brain tumor in adults. New drug design and development is still a major challenge for glioma treatment. Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a novel antitumor role in various tumors and exhibits multiple molecular functions, especially autophagic regulation. However, whether nitazoxanide-associated autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed to explore the underlying molecular mechanism of nitazoxanide in glioblastoma. Our results showed that nitazoxanide suppressed cell growth and induced cell cycle arrest in glioblastoma by upregulating ING1 expression with a favorable toxicity profile. Nitazoxanide inhibited autophagy through blockage of late-stage lysosome acidification, resulting in decreased cleavage of ING1. A combination with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of nitazoxanide in glioblastoma cells. Taken together, these findings indicate that nitazoxanide as an autophagy inhibitor induces cell cycle arrest in glioblastoma via upregulated ING1 due to increased transcription and decreased post-translational degradation by late-stage autophagic inhibition.

Cryptosporidium causes significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here we show that amixicile, a highly selective water soluble derivative of NTZ diminishes Cryptosporidium severity in a malnourished mouse model despite a lack of direct anti-cryptosporidial activity. We suggest that amixicile; by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology.

Clinical efficacy of cidofovir for treatment of adenovirus-related disease is limited and toxicity is a major concern.….

The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor involved in all phases of drug metabolism and disposition. However, recently it's been implicated in energy metabolism, tumor progression, and cancer therapy as well. It is, therefore, important to identify compounds that induce hCAR activation to predict drug-drug interactions and potential therapeutic usage. In this study, we screen the Tox21 10,000 compound collection to characterize hCAR activators. A novel structural cluster of compounds was identified, which included nitazoxanide and tenonitrozole, while known structural clusters, such as flavones and prazoles, were also detected. Four compounds, neticonazole, diphenamid, phenothrin, and rimcazole, have been identified as novel hCAR activators, one of which, rimcazole, shows potential selectivity towards hCAR over its sister receptor, the pregnane X receptor (PXR). All four compounds translocated hCAR from the cytoplasm into the nucleus demonstrating the first step to CAR activation. Profiling these compounds as hCAR activators would enable an estimation of drug-drug interactions, as well as identify prospective therapeutically beneficial drugs.

Amebiasis or amoebic dysentery is a common parasitic enteral infection. It is caused by any of the amoebas of the Entamoeba group. Amoebiasis may present with no symptoms or mild to severe symptoms including abdominal pain, diarrhea, or bloody diarrhea. Severe complications may include inflammation and perforation resulting in peritonitis. People affected may develop anemia. If the parasite reaches the bloodstream, it can spread through the body and end up in the liver causing amoebic liver abscesses. Liver abscesses can occur without previous diarrhea. Diagnosis is typically by stool examination using a microscope. An increased WBC count may be present. The most accurate test is specific antibodies in the blood. Prevention of amoebiasis is by improved sanitation. Two treatment options are possible, depending on the location. Amoebiasis in tissue is treated with metronidazole, tinidazole, nitazoxanide, dehydroemetine or chloroquine. A luminal infection is treated with diloxanide furoate or iodoquinoline. Effective treatment may require a combination of medications. Infections without symptoms require treatment, but infected individuals can spread the parasite to others. Amoebiasis is present all over the world. Each year, about 40,000 to 110,000 people die from amoebiasis infection.