Leishmania donovani modulates host miRNAs regulating cholesterol biosynthesis for its survival.

Cholesterol reduction by intracellular protozoan parasite Leishmania donovani (L. donovani), causative agent of leishmaniasis, impairs antigen presentation, pro-inflammatory cytokine secretion and host-protective membrane-receptor signaling in macrophages. Here, we studied the miRNA mediated regulation of cholesterol biosynthetic genes to understand the possible mechanism of L.

Rehabilitating a severely worn dentition with removable prosthodontics.

In the next part of this series on tooth wear management, we discuss the indications and clinical stages for the provision of removable prostheses for the treatment of severely worn and depleted dentitions. The general design features of a complex prosthesis are described for reorganised occlusal schemes and maintenance guidelines are explained. In addition, the clinical stages for three different situations are described: removable-only approaches, and combined fixed and removable in the same arch and separate arches.

Suspected Endodontic Failure in a Patient with Cleidocranial Dysplasia: A Case Report.

A patient's medical history and related dental manifestations can significantly contribute to confounding signs and symptoms leading to a diagnostic challenge. An 18-year-old female patient presented with persistent radiographic radiolucency associated with the apex of a previously treated tooth (tooth 9); asymptomatic apical periodontitis and endodontic failure were suspected. This report presents how a patient's condition of cleidocranial dysplasia had a profound effect on her dental history, which included the presence of multiple supernumerary teeth.

Recent advancements in fusion protein technologies in oncotherapy: A review.

Cancer is a complicated, adaptable, and heterogeneous disease caused by a wide variety of genetic changes that might impair ability of cells to function normally. The majority of the tumors can only be shrunk using conventional oncology therapies like chemotherapy, radiation, and surgical resection, and the tumor often recurs. The inability of conventional cancer therapies to completely destroy the Cancer Stem Cells (CSCs) that otherwise lead to therapy resistance is thus addressed by therapeutic approaches that concentrate on targeting CSCs and their micro-environmental niche.

The dental demolition derby: bruxism and its impact - part 3: repair and reconstruction.

Bruxism is a term that encompasses a range of presentations of rhythmic and repetitive muscular activity. For many, this is not a significant problem but for some, this behaviour leads to substantial impact and tissue damage that can be significant, compromising function and quality of life. This paper will review management methods for reconstructing the damaged dentition.

The dental demolition derby: bruxism and its impact - part 2: early management of bruxism.

Bruxism is a term that encompasses a range of presentations of rhythmic and repetitive muscular activity. For many, this is not a significant problem but for some, the behaviour leads to significant problems and extensive tissue damage. This is different to temporomandibular disorders.

The dental demolition derby: bruxism and its impact - part 1: background.

Bruxism may lead to changes or damage to the oral and perioral tissues. Bruxism may occur during sleep or when awake. Many patients will not require active management; however, for some, intervention is required.

Exploration of potential inhibitors for autophagy-related protein 8 as antileishmanial agents.

Leishmaniasis is considered a tropical neglected disease, which is caused by an intramacrophagic parasite, Leishmania. It is endemic in 89 different countries. Autophagy-related protein 8 (Ldatg8) is responsible for the transformation of parasites from promastigote to amastigote differentiation.

Sesamol Induces Apoptosis-Like Cell Death in .

Background: Visceral leishmaniasis (VL), caused by the protozoan parasite (), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance.

Embilica officinalis L. inhibits the growth and proliferation of Leishmania donovani through the induction of ultrastructural changes, mitochondrial dysfunction, oxidative stress and apoptosis-like cell death.

Visceral leishmaniasis (VL) is caused by a protozoan parasite, Leishmania donovani (L. donovani). It affects around 1-2 million people around the world annually.

Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L.

Dithiin diisoimides: Synthesis and their antimicrobial studies.

Sixteen derivatives of dithiin diisoimide 2a-2p have been synthesized and screened for antibacterial and antifungal activity. Compounds 2a-2g and 2i-2p are almost same or more active than gentamicine against Acinetobacter. Whereby compound 2,6-didodecyl-H,5H-pyrrolo[3',4',5,6][1,4]dithiino[2,3-c]pyrrole-1,3,5,7(2H,6H)-tetrone (2d) having zone of inhibition 20 mm against Acinetobacter is the most potent among all these compounds and can be used as lead compound for the treatment of Acinetobacter infection.

Targeting sterol alpha-14 demethylase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha-14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation.

Antileishmanial Evaluation of Bark Methanolic Extract of : and Studies.

( is an important medicinal plant, found in Africa, the Middle East, and the Indian subcontinent. Every part of the plant possesses a wide array of biologically active and therapeutically important compounds. We reported the antileishmanial activity of bark methanolic extract through antileishmanial assays and dissected the mechanism of its action through studies.

Hesperidin Targets Sterol C-24 Reductase to Fight against Leishmaniasis.

Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different and experiments.

Assessment of the Antileishmanial Potential of Leaf Extract.

has a wide array of biologically active and therapeutically important class of compounds. important drug targets, sterol 24-c methyltransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1), and nucleoside hydrolase (NH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential.

Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins.

Background And Aim: COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity.

Zygomatic implant-supported prosthodontic rehabilitation of edentulous patients with a history of cleft palate: A clinical report.

Zygomatic implants are an established treatment option in the management of the atrophic maxilla and in oncology rehabilitation, but evidence for their use in patients with a history of cleft palate is sparse. Zygomatic implants were used to retain a maxillary prosthesis in 7 edentulous patients with an unrepaired or repaired cleft lip and palate. Patient records were reviewed retrospectively to assess the survival rates.

Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response.

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.

Colono-protective Potentiality of Methanolic Bark Extract of Acacia catechu: A Medicinal Plant against 1,2-Dimethylhydrazine-Induced Toxicity in Wistar Rats.

The protective efficacy of methanolic bark extract of Acacia catechu Willd. (MEBA) against 1,2-dimethylhydrazine (DMH)-induced colon toxicity was investigated. Acacia catechu is considered one of the most potent medicines for various diseases in Ayurveda, a traditional system of Indian medicine.

Sphingosine-1-phosphate signaling in Leishmania donovani infection in macrophages.

Background: Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such as apoptosis, cell proliferation, migration, and differentiation, but its role in Leishmania donovani infection is unknown.

Methodology/ Principal Findings: In the present study, we observed that L. donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the expression of S1pr2 and S1pr3 at mRNA level.

Leishmania donovani infection differentially regulates small G-proteins.

Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishmaniasis. The parasite alters the signaling cascade in host macrophages and evades the host machinery. Small G-proteins are GTPases, grouped in 5 different families that play a crucial role in the regulation of cell proliferation, cell survival, apoptosis, intracellular trafficking, and transport.

Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism and therapeutic strategies.

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment.