Molecular Investigation of the Association Among Common Interleukin-6 Polymorphism and Human Papillomavirus Genotypes with Cervical Cancer Among Iranian Women.

Cervical cancer is the fourth most commonly identified cancer and the third important reason for cancer-related death among women in less developed nations. Aside from the human papillomavirus (HPV), the host genetic factors, especially some polymorphisms in the interleukin 6 (IL-6) gene, might relate to the risk of cervical cancer. This study aims to investigate the molecular investigation of HPV infection and its association with the common polymorphism of IL-6 in cervical carcinoma in Iran. This case-control study collected 62 precancerous and cancerous lesions and 62 healthy samples from cancer-free women, subsequent negative colposcopy, and cervical cytology. The frequency of HPV genotypes and the genotyping of IL-6 rs1800795 and rs1800796 were done by different PCR techniques. Results were analyzed using the Epi Info version 7, 2012, with the χ2 test. Compared with cervical intraepithelial neoplasia grade 1 (CINI), the HPV positivity rate is saliently higher in CINII/III and squamous cell carcinoma (SCC) (56.25%, 66.66%, and 73.63%, respectively, p < 0.001). The HPV positivity rate is also higher in SCC in comparison with CINII/III (p < 0.01). Furthermore, the most detected HPV genotypes were HPV16 and 33 in CINI; HPV16, 31, and 35 in CINII/III; and HPV16 and 18 in SCC groups. HPV16 was the most commonly detected genotype in CINI, CINII/III, and SCC, accounting for 44.44%, 50%, and 71.42%, respectively. In addition, the frequency of GG, CG, and CC genotypes from rs1800795 polymorphism was 0.58, 0.32, and 0.10, respectively (p = 0.033), but in the control group, it was 0.70, 0.27, and 0.03, respectively. The findings suggest that HPV16 plays an important role in the emergence of cervical lesions in Iranian patients. As a result, rs1800795 CC genotype and HPV might increase cervical cancer risk in Iranian women.

Structural evolution of Delta lineage of SARS-CoV-2.

One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.

Peptidomimetics in cancer targeting.

The low efficiency of treatment strategies is one of the main obstacles to developing cancer inhibitors. Up to now, various classes of therapeutics have been developed to inhibit cancer progression. Peptides due to their small size and easy production compared to proteins are highly regarded in designing cancer vaccines and oncogenic pathway inhibitors. Although peptides seem to be a suitable therapeutic option, their short lifespan, instability, and low binding affinity for their target have not been widely applicable against malignant tumors. Given the peptides' disadvantages, a new class of agents called peptidomimetic has been introduced. With advances in physical chemistry and biochemistry, as well as increased knowledge about biomolecule structures, it is now possible to chemically modify peptides to develop efficient peptidomimetics. In recent years, numerous studies have been performed to the evaluation of the effectiveness of peptidomimetics in inhibiting metastasis, angiogenesis, and cancerous cell growth. Here, we offer a comprehensive review of designed peptidomimetics to diagnose and treat cancer.

An overview of Betacoronaviruses-associated severe respiratory syndromes, focusing on sex-type-specific immune responses.

Emerging beta-coronaviruses (ß-CoVs), including Severe Acute Respiratory Syndrome CoV-1 (SARS-CoV-1), Middle East Respiratory Syndrome-CoV (MERS-CoV), and Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2, the cause of COVID19) are responsible for acute respiratory illnesses in human. The epidemiological features of the SARS, MERS, and new COVID-19 have revealed sex-dependent variations in the infection, frequency, treatment, and fatality rates of these syndromes. Females are likely less susceptible to viral infections, perhaps due to their steroid hormone levels, the impact of X-linked genes, and the sex-based immune responses. Although mostly inactive, the X chromosome makes the female's immune system more robust. The extra immune-regulatory genes of the X chromosome are associated with lower levels of viral load and decreased infection rate. Moreover, a higher titer of the antibodies and their longer blood circulation half-life are involved in a more durable immune protection in females. The activation rate of the immune cells and the production of TLR7 and IFN are more prominent in females. Although the bi-allelic expression of the immune regulatory genes can sometimes lead to autoimmune reactions, the higher titer of TLR7 in females is further associated with a stronger anti-viral immune response. Considering these sex-related differences and the similarities between the SARS, MERS, and COVID-19, we will discuss them in immune responses against the ß-CoVs-associated syndromes. We aim to provide information on sex-based disease susceptibility and response. A better understanding of the evasion strategies of pathogens and the host immune responses can provide worthful insights into immunotherapy, and vaccine development approaches.