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Topic Review
History of Programmed Death-Ligand 1 in Malignant Melanoma
Programmed death-ligand 1 (PD-L1) is the primary ligand of the receptor programmed death-1 (PD-1) which is constitutively expressed or activated in myeloid, lymphoid (T, B and NK), normal epithelial cells, and cancer. The PD-1/PD-L1 interaction is crucial for the physiological development of immunological tolerance but also in the development of the cancer. Among these, malignant melanoma represents a tumour in which the immunohistochemical expression of PD-L1 is important to guide future therapeutic choices based on the presence/absence of expression.
  • 257
  • 25 Jun 2023
Topic Review
ESAT-6 a Major Virulence Factor of Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) virulence relies on its ability to manipulate host macrophages, where it establishes intracellular niches to cross mucosal barriers and avoid pathogen destruction. First, Mtb subverts the endocytic pathway, preventing phagolysosome fusion and proteolytic digestion. Second, it activates innate immune responses to induce its transmigration into the lung parenchyma. There, infected macrophages attract more permissive cells, expanding intracellular niches. Mtb induces the adaptive responses that stimulate its containment and encourage a long life inside granulomas. Finally, the pathogen induces necrotic cell death in macrophages, granuloma destruction, and lung cavitation for transmission. Common to all these events is the major virulence factor: the “early secreted antigenic target of 6 kDa” (ESAT-6, also called EsxA). The loss or gain of mycobacterial virulence is closely linked to the ability of mycobacteria to produce and secrete ESAT-6, and the extension of virulence is correlated with the amount of protein secreted. ESAT-6 secretion from the bacilli requires both the expression of the esx-1 locus for the type VII secretion apparatus and the transcription of both the ESAT-6 gene (esxA) and the culture filtrate protein 10 (CFP-10) gene (esx-B) contained in the RD1 region of the genome. In addition, it requires the protein EspA, which is not encoded in the esx-1 locus but in the extended espACD operon adjacent to RD8. All species and strains deleted in the esx-1 locus, the internal RD1 region, or the esx-1 extended locus espACD exhibit an attenuated phenotype. Mutants with deletions on ESX-1 of Mtb are attenuated in virulence, translating into reduced survival of mycobacteria in cultured macrophages or in experimental animal models of TB. Curiously, the saprophyte species M. smegmatis (Ms) also encodes for an ESX-1 apparatus; however, it does not appear to confer Ms virulence capabilities, as demonstrated by its inability to survive in human macrophages or in amoeba in the environment. Predatory amoeba may have contributed to the evolutionary pressure that selected mycobacterial pathogens for intracellular survival. 
  • 421
  • 25 Jun 2023
Topic Review
Uric Acid Electroanalysis
Uric acid is a metabolic product that results from degradation of purines in the liver. Usually, uric acid is identified from biological fluids, human serum and urine through conventional methods, such as spectroscopy, chromatography, electrochemistry, membrane capillary electrophoresis and spectrophotometric methods, including uricase enzymatic reactions. Importantly, uric acid determination opens the possibility of early intervention in cases of hyperuricemia and preventing the degradation of renal function.
  • 630
  • 25 Jun 2023
Topic Review
Celiac Disease and Type 1 Diabetes Mellitus
Celiac disease (CeD) is associated with type 1 diabetes mellitus (T1DM), and both have the same genetic background. Type 1 diabetes mellitus (T1DM), an autoimmune disease, is caused by insulin deficiency due to destruction of the insulin-producing pancreatic beta cells.
  • 571
  • 25 Jun 2023
Topic Review
Cerebral Sinus Vein Thrombosis and Gender
Cerebral sinus venous thrombosis (CSVT) is a relatively rare acute disorder of cerebral circulation, but it can potentially be associated with serious sequelae and a poor prognosis. The neurological manifestations associated with it are often not adequately taken into consideration given the extreme variability and nuances of its clinical presentation and given the need for radiological methods suitable for this type of diagnosis. CSVT is usually more common in women, but so far there are little data available in the literature on sex-specific characteristics regarding this pathology. CSVT is the result of multiple conditions and is therefore to be considered a multifactorial disease where at least one risk factor is present in over 80% of cases.
  • 243
  • 25 Jun 2023
Topic Review
New Potential Heterocyclic Molecular Targeted Drugs
Heterocyclic compounds, which are made up of both carbon and non-carbon atoms, serve as a crucial structural foundation for numerous chemicals with pharmacological and biological value. The research on heterocyclic compounds is an important part of organic chemistry and is utilized extensively in many industries, especially medicine. Heterocyclic compounds serve as the main active ingredient in a variety of pharmaceuticals, including analgesics, anti-inflammatory drugs, anti-tubercular drugs, antihypertensives, antidepressants, and even anticancer drugs. Many novel heterocyclic targeted drugs have emerged.Molecular targeted therapy is a key element of the new era of comprehensive multidisciplinary cancer treatment. A considerable number of molecular targeted medications have been created as part of the development of targeted therapy. 
  • 291
  • 25 Jun 2023
Topic Review
Intranasal Nanoemulsions for the Management of Brain Diseases
The intranasal pathway (olfactory and trigeminal nerves) lets the entry of various bioactive agents circumvent the hepatic first-pass effect, thus targetingneurological diseases. Several investigations and research have suggested the vital role ofdrug-loaded nanoemulsions in the mitigation of countless brain disorders proves to be a potential alternative to oral drug delivery systems. Further, mucoadhesive polymer enriched nanoemulsion prolongs residence time and therapeutic effect by weakening rapid clearance from the nasal mucosa. Obtained nanoemulsion possessed ~68 nm average particle size and positive zeta potential (~13 mV). The formulation exhibited 85.5% encapsulation efficiency and 72 h prolonged in vitro release of luteolin. Ex vivo performed Baker–Lonsdale kinetic model depicted approximately six times higher permeation across the nasal mucosa. Moreover, pharmacokinetic studies of the single dose administered intranasal nanoemulsion revealed a tentimes higher drug half-life and nearly a four times higher luteolin biodistribution in brain tissues that further suggested potential usage of developed chitosan-coated luteolin nanoemulsion for the management of brain neuroblastoma. 
  • 400
  • 25 Jun 2023
Topic Review
Therapeutic Potential of Orally Administered Rubiscolin-6
Rubiscolins are naturally occurring opioid peptides derived from the enzymatic digestion of the ribulose bisphosphate carboxylase/oxygenase protein in spinach leaves. They are classified into two subtypes based on amino acid sequence, namely rubiscolin-5 and rubiscolin-6. In vitro studies have determined rubiscolins as G protein-biased delta-opioid receptor agonists, and in vivo studies have demonstrated that they exert several beneficial effects via the central nervous system. The most unique and attractive advantage of rubiscolin-6 over other oligopeptides is its oral availability. Therefore, it can be considered a promising candidate for the development of a novel and safe drug.
  • 329
  • 25 Jun 2023
Topic Review
Bulk-Fill Resins versus Conventional Resins
Composite resins have become the material of choice for the restoration of posterior teeth. Although bulk-fill resins represent a tempting alternative due to their lower complexity and faster use, some dentists are reluctant to use this material. 
  • 412
  • 25 Jun 2023
Topic Review
Skin Pigmentation
Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients’ physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison’s disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. 
  • 736
  • 25 Jun 2023
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