Unraveling the Molecular Mechanisms Involved in HCV-Induced Carcinogenesis.

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. The virus promotes the development of carcinogenesis through indirect and direct molecular mechanisms such as chronic inflammation, oxidative stress, steatosis, genetic alterations, epithelial-mesenchymal transition, proliferation, and apoptosis, among others. Recently, direct-acting antivirals (DAAs) showed sustained virologic response in 95% of cases. Nevertheless, patients treated with DAAs have reported an unexpected increase in the early incidence of Hepatocellular carcinoma (HCC). Studies suggest that HCV induces epigenetic regulation through non-coding RNAs, DNA methylation, and chromatin remodeling, which modify gene expressions and induce genomic instability related to HCC development that persists with the infection's clearance. The need for a better understanding of the molecular mechanisms associated with the development of carcinogenesis is evident. The aim of this review was to unravel the molecular pathways involved in the development of carcinogenesis before, during, and after the viral infection's resolution, and how these pathways were regulated by the virus, to find control points that can be used as potential therapeutic targets.

Diethylcarbamazine as potential treatment of COVID-19 lung fibrosis.

Diethylcarbamazine, the antiparasitic drug, also possesses anti-inflammatory and immunomodulatory activities. The anti-fibrotic activity of diethylcarbamazine makes it a potential candidate to treat coronavirus disease 2019 (COVID-19)-related pulmonary fibrosis. Experimental and clinical studies should assess this possible effect.

Lack of IgG antibody seropositivity to Borrelia burgdorferi in patients with Parry-Romberg syndrome and linear morphea en coup de sabre in Mexico.

BACKGROUND: Progressive hemifacial atrophy or Parry-Romberg Syndrome (PRS) is a rare, acquired, progressive dysplasia of subcutaneous tissue and bone characterized by unilateral facial involvement. Its etiology is unknown, but theories about its pathogenesis include infectious, degenerative, autoimmune, and traumatic causes among others. The causal relationship of PRS and linear morphea en coup de sabre (LMCS) with Borrelia burgdorferi infection remains controversial. Our goal was to serologically determine anti-B. burgdorferi antibodies in patients diagnosed with PRS and LMCS to establish a possible association as a causative agent. METHODS: We conducted a serology study with patients belonging to a group of 21 individuals diagnosed with PRS, six with LMCS, and 21 matched controls. Anti-Borrelia IgG antibodies were determined by ELISA. A descriptive statistical analysis and Fischer's exact test were done. RESULTS: In serological tests, only two cases had borderline values and were further analyzed by Western blot with non-confirmatory results. For both the PRS and LMCS group, the association test was not significant, suggesting a lack of association between PRS or LMCS and the presence of anti-Borrelia antibodies. CONCLUSION: In Mexico there are no previous studies on Borrelia infection and its relationship between PRS or LMCS. Our result showed a lack of association of either clinical entities with anti-Borrelia-antibodies. Former reports of this association may suggest coincidental findings without causal relationship.

Immunomodulatory activity of diethylcarbamazine on humoral, cellular cytokine response and respiratory burst in BALB/c mice.

Diethylcarbamazine (DEC) is an anthelmintic piperazine derivative drug with putative immunomodulating properties, including increased platelet and granulocyte adhesion to parasites and enhanced production of cytokines. To further analyse these properties in a well-established animal model, we evaluated the effect of DEC on antibody, cellular cytokine response and respiratory burst in BALB/c mice. Animals were challenged with a thymus-dependent (tetanus toxoid, (TT)) and with a thymus-independent (lipopolysaccharide, (LPS)) antigen and treated with DEC for seven days with two different doses (50 mg/day and 500 mg/day). Serum was assessed for antibody production at 0, 4, 7, 14, 21 and 28 days after stimulation and at 0, 24 and 48 h for IL-2, IFN-γ, IL-10 and IL-12 release. Respiratory burst of neutrophils and monocytes from peripheral blood was measured by flow cytometry. We found low-dose treatment with DEC enhanced cytokine production vs. TT and antibody production vs. LPS, whereas a higher dose enhanced significantly the respiratory burst of both polymorphonuclear leukocytes and monocytes, with a significant higher effect on the former. Our results suggest a stimulating, dose-dependent immunomodulatory effect of DEC with a higher effect on the phagocytic cells.