During cartilage development, the lineage commitment and condensation of stem cells into chondrocytes and their differentiation involves a ubiquitous signaling cascades and huge numbers of transcriptional factors. The kinetic requirements and the stoichiometry for the expression of key transcriptional factors are relevant and must be met to form proper and functionally competent cartilage tissue. More interestingly also, an exact and precise spatio-temporal distribution of these molecules are as necessary in the proper tissue morphogenesis and patterning as the relevant physical conditions and micro environmental forces playing at the background during embryogenesis. A milestone of experimental achievements has been obtained over the years on several signaling pathways involved in cartilage development. Several fate determining transcriptional factors has also been investigated and determined with regards to the transition of stem cells (pluripotent, embryonic, etc.) into chondrocytes. These transcriptional factors serve as master controllers in chondrocytes proliferation and hypertrophy. Concerns that variability in signaling and transcriptional factors have detrimental effect on cartilage formation and could potentiate most cartilage related diseases have led most scientists to investigate the role of signaling molecules and transcriptional factors implicated in osteoarthritis, rheumatoid arthritis, and other cartilage degenerative diseases. On bases of spatio-temporal distribution of transcriptional factors, there exist functional overlaps, hence, it is difficult to draw a hard line of demarcation of roles at each point of the cell’s life, nonetheless, it is also markedly established that some factors are skewed to the chondrocyte’ survival and proliferation, and others known for their master’s role in the cell’s apoptotic, necrotic and senescence. Here we review some published works on selected signaling pathways and transcriptional factors that are preferentially expressed in chondrogenic cells and their role as major players in cartilage formation, cartilage diseases, along with some highlights of unique signaling molecules that are indispensable in cartilage tissue regeneration and management.

Salmonella can cause acute and chronic infections in humans. Salmonella species are known to cause food poisoning and other diseases in developing countries. Their role in the pathogenesis of these diseases has received increased international attention. Despite numerous advances in sanitation, they still can infect humans and cause outbreaks in developed countries. For example, Salmonella causes about 1.2 million illnesses in the US each year with over 450 deaths. Additionally, Salmonella outbreaks cause significant losses to chicken producers globally. The Salmonella species is also prone to acquiring resistance to various classes of antibiotics. Hence, the need for a paradigm shift from antibiotics to bacteriophages to manage, control and treat bacterial infections. The ɛ34 phage belongs to Podoviruses and categorized into the P22-like phages. The P22-like phages include ɛ34, ES18, P22, ST104, and ST64T. In this work, we investigated the antibacterial property of ɛ34 phage tailspike protein against Salmonella newington (S. newington). We demonstrate here that, the phage’s tailspike protein enzymatic property as a LPS hydrolase synergizes with Vero Cell culture supernatant in killing S. newington. Using decellularized cartilage scaffold as an ex vivo tissue model, the ɛ34 TSP protected the scaffold from S. newington biofilm formation. Computational analysis of the ɛ34 TSP interaction with membrane proteins of S. newington demonstrated a higher probability (0.7318) of binding to ompA of S. newington, and when docked to ompA extracellular component, it produced a high free energy of -11.3kcal/mol. We also demonstrate the resistance/sensitivity of the tailspike to the digestive enzyme trypsin. The data obtained in this work indicates that the trypsin resistant tailspike protein of Ɛ34 phage can be formulated as a novel antibacterial agent against S. newington.

Infection by human immunodeficiency virus type I (HIV-1) requires virus particle binding to host cell-surface receptor CD4 via the viral envelope glycoprotein gp120. HIV-1 therapy and prevention efforts involve development of mimetic or recombinant gp120 vaccines or deployment of antiviral agents that target specific epitopes of gp120. The unliganded conformational state of gp120 is closed, whereas the CD4-bound state is open. However, in between, there exist dynamic conformational states, indicating intrinsically flexible region(s) of structural dynamics, imposing a structural challenge for developing drug or antibody targets. Known conformational states of gp120 were determined by X-ray crystallographic and cryo-electron microscopy, and neither method captures the population of gp120 species arising from conformational plasticity, motions, and transitions. gp120 plasticity brings up several important questions. How will differences in conformation affect receptor binding, antibody recognition, and neutralization? Which regions are crucial for gp120 structural plasticity? How could structural dynamics influence HIV-1 evasiveness against host immunity and drugs or vaccines, and facilitate the viral entry into its host? This review explores the structural constraints presented by conformational states of the glycoprotein to antibodies or drugs and how these conformational states provide structural avenues for the virus to escape neutralizing agents and evade host immunity.

Calcium signaling and lipid metabolism are crucial in the infection processes of Apicomplexans parasites. Thus, enzymes involved in these processes can be drug targets against Apicomplexans. For example, in malaria infection, in-depth research into lipid metabolic pathways is crucial in understanding the parasite's infection cycle, particularly during its erythrocytic infection cycle, which has been demonstrated to be a critical stage during the disease progression. Most enzymes that play critical roles in lipid synthesis and calcium signaling have been extensively studied; nonetheless, a vast knowledge gap still exists, especially on specific enzymes and their roles in the transmission and progression of the Apicomplexan parasites. Many types of infections caused by Apicomplexans are life-threatening and hard to treat. These intracellular parasites proliferate within parasitophorous vacuoles in their host cells. As the parasites multiply, they need to meet their high demand for nutrients such as amino acids and lipids. They can acquire nutrients through scavenging and biosynthesis. This review summarizes a few interesting, unique pathways in selected Apicomplexa and how such unique pathways can be targets for drugs.