Human Papilloma Virus-Infected Cells.

Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the tongue, skin, the lungs, among other tissues. HPV infection may or may not be associated with the development of cancer, where HPVs not related to cancer are defined as low-risk HPVs and are associated with papillomatosis disease. In contrast, high-risk HPVs (HR-HPVs) are associated with developing cancers in areas that HR-HPV infects, such as the cervix. In general, infection of HPV target cells is regulated by specific molecules and receptors that induce various conformational changes of HPV capsid proteins, allowing activation of HPV endocytosis mechanisms and the arrival of the HPV genome to the human cell nucleus. After the transcription of the HPV genome, the HPV genome duplicates exponentially to lodge in a new HPV capsid, inducing the process of exocytosis of HPV virions and thus releasing a new HPV viral particle with a high potential of infection. This infection process allows the HPV viral life cycle to conclude and enables the growth of HPV virions. Understanding the entire infection process has been a topic that researchers have studied and developed for decades; however, there are many things to still understand about HPV infection. A thorough understanding of these HPV infection processes will allow new potential treatments for HPV-associated cancer and papillomatosis. This chapter focuses on HPV infection, the process that will enable HPV to complete its HPV life cycle, emphasizing the critical role of different molecules in allowing this infection and its completion during the HPV viral life cycle.

Characterization of cornea donors at a tissue center in the city of Medellin, Colombia.

The cornea transplant is considered the most frequently performed type of transplant in the world, with a demand that has been increasing in recent years. An observational descriptive study was conducted, focusing on the ocular tissue extracted from cadaveric donors from January 2019 to December 2021 at the Red Cross Eye Bank in Medellin, Colombia. This is the first epidemiological characterization of corneal donor tissues within the eye banks of our city, where high rates of violence-related deaths explain that tissue donors are mostly young individuals. This, in turn, results in excellent counts of endothelial cells and tissue viability in their microscopic studies. Additionally, there are lower rates of discarded tissues compared to similar studies.

Nuclear factor erythroid 2-related factor 2 in human papillomavirus-related cancers.

High-risk human papillomavirus (HR-HPV) infection is a necessary cause for the development of cervical cancer. Moreover, HR-HPV is also associated with cancers in the anus, vagina, vulva, penis and oropharynx. HR-HPVs target and modify the function of different cell biomolecules, such as glucose, amino acids, lipids and transcription factors (TF), such as p53, nuclear factor erythroid 2-related factor 2 (Nrf2), among others. The latter is a master TF that maintains redox homeostasis. Nrf2 also induces the transcription of genes associated with cell detoxification. Since both processes are critical for cell physiology, Nrf2 deregulation is associated with cancer development. Nrf2 is a crucial molecule in HPV-related cancer development but underexplored. Moreover, Nrf2 activation is also associated with resistance to chemotherapy and radiotherapy in these cancers. This review focusses on the importance of Nrf2 during HPV-related cancer development, resistance to therapy and potential therapies associated with Nrf2 as a molecular target.

Antioxidant/anti-inflammatory effect of Mg2+ in coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi-organ failure in severe cases. Magnesium (Mg2+ ) regulates many processes, including antioxidant and anti-inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg2+ has an anti-inflammatory response by reducing the levels of nuclear factor kappa B (NF-κB), interleukin (IL) -6, and tumor necrosis factor alpha. Furthermore, Mg2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID-19. This narrative review will address Mg2+ deficiency associated with a worse disease prognosis, Mg2+ supplementation as a potent antioxidant and anti-inflammatory therapy during and after COVID-19 disease, and suggest that randomised controlled trials are indicated.

α-Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple-negative breast cancer model.

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor; therefore, TNBC lacks targeted therapy, and chemotherapy is the only available treatment for this illness but causes side effects. A putative strategy for the treatment of TNBC could be the use of the polyphenols such as α-Mangostin (α-M), which has shown anticancerogenic effects in different cancer models and can modulate the inflammatory and prooxidant state in several pathological models. The redox state, oxidative stress (OS), and oxidative damage are highly related to cancer development and its treatment. Thus, this study aimed to evaluate the effects of α-M on redox state, mitochondrial metabolism, and apoptosis in 4T1 mammary carcinoma cells. We found that α-M decreases both protein levels and enzymatic activity of catalase, and increases reactive oxygen species, oxidized proteins and glutathione disulfide, which demonstrates that α-M induces oxidative damage. We also found that α-M promotes mitochondrial dysfunction by abating basal respiration, the respiration ligated to oxidative phosphorylation (OXPHOS), and the rate control of whole 4T1 cells. Additionally, α-M also decreases the levels of OXPHOS subunits of mitochondrial complexes I, II, III, and adenosine triphosphate synthase, the activity of mitochondrial complex I as well as the levels of peroxisome proliferator-activated receptor-gamma co-activator 1α, showing a mitochondrial mass reduction. Then, oxidative damage and mitochondrial dysfunction induced by α-M induce apoptosis of 4T1 cells, which is evidenced by B cell lymphoma 2 decrease and caspase 3 cleavage. Taken together, our results suggest that α-M induces OS and mitochondrial dysfunction, resulting in 4T1 cell death through apoptotic mechanisms.

Mitochondrial Impairment: A Link for Inflammatory Responses Activation in the Cardiorenal Syndrome Type 4.

Cardiorenal syndrome type 4 (CRS type 4) occurs when chronic kidney disease (CKD) leads to cardiovascular damage, resulting in high morbidity and mortality rates. Mitochondria, vital organelles responsible for essential cellular functions, can become dysfunctional in CKD. This dysfunction can trigger inflammatory responses in distant organs by releasing Damage-associated molecular patterns (DAMPs). These DAMPs are recognized by immune receptors within cells, including Toll-like receptors (TLR) like TLR2, TLR4, and TLR9, the nucleotide-binding domain, leucine-rich-containing family pyrin domain-containing-3 (NLRP3) inflammasome, and the cyclic guanosine monophosphate (cGMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway. Activation of these immune receptors leads to the increased expression of cytokines and chemokines. Excessive chemokine stimulation results in the recruitment of inflammatory cells into tissues, causing chronic damage. Experimental studies have demonstrated that chemokines are upregulated in the heart during CKD, contributing to CRS type 4. Conversely, chemokine inhibitors have been shown to reduce chronic inflammation and prevent cardiorenal impairment. However, the molecular connection between mitochondrial DAMPs and inflammatory pathways responsible for chemokine overactivation in CRS type 4 has not been explored. In this review, we delve into mechanistic insights and discuss how various mitochondrial DAMPs released by the kidney during CKD can activate TLRs, NLRP3, and cGAS-STING immune pathways in the heart. This activation leads to the upregulation of chemokines, ultimately culminating in the establishment of CRS type 4. Furthermore, we propose using chemokine inhibitors as potential strategies for preventing CRS type 4.

Redox state associated with antitumor and immunomodulatory peptides in cancer.

Cancer, a major public health problem, is the fourth cause of death in the world. While cancer mortality has decreased in recent decades due to more effective treatments, mostly based on improving antitumor immunity, some forms of cancer are resistant to these immunotherapies. A promising approach for cancer treatment involves the administration of antitumor and immunomodulatory peptides. Immunomodulatory peptides have been proved to exert antitumor and immunomodulatory effects by activating immune cells such as cytotoxic T cells, with fewer side-effects. A process closely related to the regulation of the immune system by immunomodulatory antitumor peptides is the modulation of the redox state, which has been poorly studied. This review focuses on the redox state regulated by antitumor and immunomodulatory peptides in cancer development, and on the potential of redox state as a therapy associated with these peptides in cancer treatment.

Redox-sensitive signalling pathways regulated by human papillomavirus in HPV-related cancers.

High-risk human papillomavirus (HR-HPV) chronic infection is associated with the induction of different HPV-related cancers, such as cervical, anus, vaginal, vulva, penis and oropharynx. HPV-related cancers have been related to oxidative stress (OS), where OS has a significant role in cancer development and maintenance. Surgical resection is the treatment of choice for localised HPV-related cancers; however, these malignancies commonly progress to metastasis. In advanced stages, systemic therapies are the best option against HPV-related cancers. These therapies include cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies. Nevertheless, these strategies are still insufficient. Cell redox-sensitive signalling pathways have been poorly studied, although they have been associated with the development and maintenance of HPV-related cancers. In this review, we analyse the known alterations of the following redox-sensitive molecules and signalling pathways by HR-HPV in HPV-related cancers: MAPKs, Akt/TSC2/mTORC1, Wnt/ß-Cat, NFkB/IkB/NOX2, HIF/VHL/VEGF and mitochondrial signalling pathways as potential targets for redox therapy.

Regulation of autophagy by high- and low-risk human papillomaviruses.

While high-risk human papillomavirus (HR-HPV) infection is related to the development of cervical, vulvar, anal, penile and oropharyngeal cancer, low-risk human papillomavirus (LR-HPV) infection is implicated in about 90% of genital warts, which rarely progress to cancer. The carcinogenic role of HR-HPV is due to the overexpression of HPV E5, E6 and E7 oncoproteins which target and modify cellular proteins implicated in cell proliferation, apoptosis and immortalization. LR-HPV proteins also target and modify some of these processes; however, their oncogenic potential is lower than that of HR-HPV. HR-HPVs have substantial differences with LR-HPVs such as viral integration into the cell genome, induction of p53 and retinoblastoma protein degradation, alternative splicing in HR-HPV E6-E7 open reading frames, among others. In addition, LR-HPV can activate the autophagy process in infected cells while HR-HPV infection deactivates it. However, in cancer HR-HPV might reactivate autophagy in advance stages. Autophagy is a catabolic process that maintains cell homoeostasis by lysosomal degradation and recycling of damaged macromolecules and organelles; nevertheless, depending upon cellular context autophagy may also induce cell death. Therefore, autophagy can contribute either as a promotor or as a suppressor of tumours. In this review, we focus on the role of HR-HPV and LR-HPV in autophagy during viral infection and cancer development. Additionally, we review key regulatory molecules such as microRNAs in HPV present during autophagy, and we emphasize the potential use of cancer treatments associated with autophagy in HPV-related cancers.

Chronic kidney disease is a very significant comorbidity for high risk of death in patients with COVID-19 in Mexico.

Chronic kidney disease (CKD) is a recognized public health problem and key determinant of poor health outcomes. In Mexico, this condition has been associated with high and significant risk of death in COVID-19 patients; however, not enough attention has been given to the vulnerable population as the increasing numbers and fatality rates suggest. This study evaluated the effect of interaction between CKD condition and other risk factors (sex, diabetes, hypertension and obesity) on the survival rate of positive patients for COVID-19 in Mexico. The results from this study support that CKD patients is a population at high risk for mortality for COVID-19 and that COVID-19 positive inpatients with CKD and diabetes are highly vulnerable to death.

Bioaccessibility of polyphenols and antioxidant capacity of fresh or minimally processed modern or traditional lettuce (Lactuca sativa L.) varieties.

Modern city lifestyle is characterized by an increased demand for fresh or minimally processed foods. Lettuce (Lactuca sativa L.), mainly iceberg lettuce, is the main vegetable used during the manufacture of fresh-cut salads. The current study evaluated the phenolic content and antioxidant activity of ten fresh and minimally processed lettuce varieties. The phenolic content of selected lettuce samples varied significantly among varieties. Although a higher phenolic content was observed in modern lettuce varieties, when compared to the traditional ones (except for the landrace Francès 219/855), the antioxidant capacity of modern and traditional lettuce varieties was similar. Minimal processing followed by storage for a 7-day period led to an increased phenolic content in varieties Rutilaï RZ, Abago RZ, Maravilla LS044, Francès 219/855, Negre borratger 386/935, and D'hivern LS008, supporting the hypothesis that wounding can induce the accumulation of phenolic compounds in lettuce leaves. For example, the total phenolic content of Francès 219/855 after processing and storage increased from 8.3 to 11.3 mg/100 g (p < 0.05). Accumulation of phenolic compounds after minimal processing was not observed in all the studied samples, suggesting that this effect could be matrix-dependant. The amount of bioaccessible polyphenols was higher after minimal processing and storage. Indeed, the amount of bioaccessible polyphenols after a simulated gastrointestinal digestion of fresh or minimally processed Pelikan lettuce was calculated as 32.6 or 43.3 mg/100 g respectively (p < 0.05), suggesting that the increased amount of polyphenols caused by processing and storage can also lead to a higher amount of bioaccessible phenolic compounds.

Dynamical phase transition in spike neuronal firing patterns of hippocampal cells.

There is increasing evidence that the brain resides in a state of criticality. The purpose of the present work is to characterize the dynamics of individual hippocampal CA1 pyramidal cells and to investigate how it is influenced by changes in Kv7.2/7.3 (M-channel) ion channel modulation, which is known to be key in determining the neuronal excitability. We show that the resting activity of CA1 neurons exhibit random dynamics with low information content, while changes in M-channel modulation move the neuronal activity near a phase transition to richer non-trivial dynamics. We interpret these results as the basis upon which the state of self-organized criticality is built.

Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia.

PURPOSE: The main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied on patients from Andean region. Bogotá and Medellin presented its own battery of mutations. This study aims to identify mutations in BRCA1-2 genes in women with familial breast cancer from different regions of Colombia. METHODS: One hundred four families with a history of breast cancer were sampled in different regions of Colombia, and the BRCA1 gene and exon 11 of the BRCA2 gene were sequenced. To predict the possible effects of sequence alterations found in protein function, different bioinformatics tools were used. RESULTS: A total of 33 variants were found; 18 in BRCA1 and 15 in BRCA2, of which 15 are unique variants of Colombia. In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic. Both the mutations as the variants of unknown clinical significance, in their great majority, presented a specific region distribution and they were different from those reported in previous studies. CONCLUSIONS: In this study we report the BRCA1 and BRCA2 spectrum of mutations and their distribution by regions in Colombia. Our results may help to design a diagnostic test including recurrent mutations for screening high risk to breast cancer families in Colombia.

Living biomass supported on a natural-fiber biofilter for lead removal.

Living biomass biofilters constitute an excellent alternative for heavy metal bioremediation. In situ biomass and exopolysaccharides production involve a crucial advantage over other bioremediation alternatives such as lignocellulosic biomass-based materials. In this study, a biofilm-forming bacterium was isolated from an ambient exposed to heavy metals. Bacterial biomass was inoculated on a biofilter packed with Furcraea andina fibers. The goal was to develop a continuous low-cost biofilter to remove low-to-moderate concentrations of Pb2+. Adsorption equilibrium and kinetics were determined for the fibers and the biofilm developed on the fibers. Biofilm presence had positive effects on the maximum adsorption capacity and the process kinetics. Biofilters packed with 20 g of F. andina fibers, with and without living biomass biofilm, were evaluated under continuous inflow of Pb2+ (325 mg/day) at a concentration of 50 mg/L. The best results were obtained with the biofilm-fiber biofilter where total adsorption on Pb2+ were observed for 72 h. Maximum absorption capacity was 48.75 mg/g at pH = 7.

Clinical assessment and brain findings in a cohort of mothers, fetuses and infants infected with ZIKA virus.

BACKGROUND: Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited. OBJECTIVES: Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations. STUDY DESIGN: This is a longitudinal cohort study of Zika virus-infected pregnancies from a single institution in Colombia. Clinical and imaging findings of patients with laboratory-confirmed Zika virus infection and fetal brain anomalies were the focus of this study. Patients underwent monthly fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging. Postnatally, infant brain assessment was offered by the use of ultrasound imaging, magnetic resonance imaging, and/or computed tomography. Fetal head circumference measurements were compared with different reference ranges with <2 or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal and infant magnetic resonance imaging images were processed to obtain a quantitative brain volumetric assessment. Diffusion weighted imaging sequences were processed to assess brain microstructure. Anthropometric, neurologic, auditory, and visual assessments were performed postnatally. Histopathologic assessment was included if patients opted for pregnancy termination. RESULTS: All women (n=214) had been referred for Zika virus symptoms during pregnancy that affected themselves or their partners or if fetal anomalies that are compatible with congenital Zika virus syndrome were detected. A total of 12 pregnant patients with laboratory confirmation of Zika virus infection were diagnosed with fetal brain malformations. Most common findings that were assessed by prenatal and postnatal imaging were brain volume loss (92%), calcifications (92%), callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly (92%). Results from fetal brain volumetric assessment by magnetic resonance imaging showed that 1 of the most common findings associated with microcephaly was reduced supratentorial brain parenchyma and increased subarachnoid cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion coefficient values showed microstructural changes. Microcephaly was present in 33.3-58.3% of the cases at referral and was present at delivery in 55.6-77.8% of cases. At birth, most of the affected neonates (55.6-77.8%) had head circumference measurements >3 standard deviations below the mean. Postnatal imaging studies confirmed brain malformations that were detected prenatally. Auditory screening results were normal in 2 cases that were assessed. Visual screening showed different anomalies in 2 of the 3 cases that were examined. Pathologic results that were obtained from 2 of the 3 cases who opted for termination showed similar signs of abnormalities in the central nervous system and placental analyses, including brain microcalcifications. CONCLUSION: Congenital microcephaly is not an optimal screening method for congenital Zika virus syndrome, because it may not accompany other evident and preceding brain findings; microcephaly could be an endpoint of the disease that results from progressive changes that are related to brain volume loss. Long-term studies are needed to understand the clinical and developmental relevance of these findings.

Direct Lewis Acid Catalyzed Conversion of Enantioenriched N-Acyloxazolidinones to Chiral Esters, Amides, and Acids.

The identification of Yb(OTf)3 through a multivariable high-throughput experimentation strategy has enabled a unified protocol for the direct conversion of enantioenriched N-acyloxazolidinones to the corresponding chiral esters, amides, and carboxylic acids. This straightforward and catalytic method has shown remarkable chemoselectivity for substitution at the acyclic N-acyl carbonyl for a diverse array of N-acyloxazolidinone substrates. The ionic radius of the Lewis acid catalyst was demonstrated as a key driver of catalyst performance that led to the identification of a robust and scalable esterification of a pharmaceutical intermediate using catalytic Y(OTf)3.

Increasing Incidence and Prevalence of Multiple Sclerosis in Puerto Rico (2013-2016).

BACKGROUND: The incidence of multiple sclerosis (MS) has been increasing worldwide over the past decades. However, this upward trend has not been examined at the country level in Latin America and the Caribbean (LAC). The aims of this study are to examine trends of MS incidence over 4 years and to provide age- and gender-standardized incidence rate estimates for a Caribbean island. METHODS: Data from the Puerto Rico (PR) MS Foundation's registry was used to identify all newly diagnosed MS cases between 2013 and 2016. MS patients were 18 years and older and met the 2010 revised McDonald criteria. Age- and gender-standardized incidence rates were estimated. RESULTS: A total of 583 new MS cases were diagnosed in PR from 2013 to 2016. The age- and gender-standardized MS incidence rate for PR increased from 6.1/100,000 in 2013 to 6.7/100,000 in 2016. The annual age-standardized MS incidence rates for females rose from 8.4/100,000 in 2013 to 9.8/100,000 in 2016 and were higher than males, which remained around 3.7/100,000. CONCLUSION: Incidence estimates for PR were higher than other LAC countries but consistent with MS increases in other world regions. Our findings tend to rule out several prior potential environmental explanations for high MS incidence rates.

Pelvic hemangiopericytoma. An unusual location of a vascular tumor.

BACKGROUND: The hemangiopericytoma is an uncommon vascular tumour. We report a case of interest because of its rarity, size and location. CASE REPORT: We present the case of a 63-year-old woman who consulted for abdominal pain. TAC, MRI and arteriography showed a pelvic mass occupying Douglas' space, displacing the uterus, bladder and sigma, with vascularisation relative to the inferior mesenteric artery and both hypogastric arteries. The vascularity of the tumour itself was selectively embolised before the mass was resected. There were no intra- or postoperative complications. Pathology confirmed the diagnosis of hemangiopericitoma. The patient is being monitored as an outpatient, with no signs of recurrence to date. DISCUSSION: The hemangiopericytoma is a tumour of the pericyte cells so it can occur in any location. The pelvic location is exceptional. The tumour may appear as nonspecific abdominal pain, show signs of compression of adjacent organs or occasionally be associated with paraneoplastic syndromes. The diagnosis is suspected via CT and angiography findings, but confirmation is only made by analysing the surgical specimen. The treatment of choice is surgery, in some cases after preoperative embolisation of the vascularisation of the mass. There is no agreement on chemo/radiotherapy as the primary treatment for hemangiopericytoma, although adjuvant radiation therapy has been found to improve local control and reduce recurrences. The prognosis is good if complete resection is achieved, with five- and 10-year survival rates between 70 and 80%, depending on the series.