Background: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First-or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. Results: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55e10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88e12.56). Conclusion: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with noncancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.

Liquorice root has been used in Europe since prehistoric times, and is well documented in written form starting with the ancient Greeks. In this review we compare the independent development of medical uses of this botanical drug in several ancient cultures, attempting to show the rationality of specific indications across different ethnic groups with different cultural backgrounds. Identical specific indications in different cultures highlight universally reproducible therapeutic effects that are beyond those of a mere placebo. In the first part of the review, historical sources dealing with liquorice (Scythian, Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have been considered. In the second part, the historical records of diseases treated with liquorice have been presented. Finally, a comparison between traditional use in and outside Europe, with the most important recent scientific studies concerning its use, is presented.

Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

The mechanisms of cisplatin resistance, one of the major limitations of current chemotherapy, has only partially been described. We previously demonstrated that cisplatin-resistant ovarian cancer cells (C13), are characterized by reduced mitochondrial activity and higher glucose-dependency when compared to the cisplatin-sensitive counterpart (2008). In this work we further characterized the role of metabolic transformation in cisplatin resistance. By using transmitochondrial hybrids we show that metabolic reprogramming of cisplatin-resistant cell is not caused by inherent mtDNA mutations. We also found that C13 cells not only present an increased glucose-uptake and consumption, but also exhibit increased expression and enzymatic activity of the Pentose Phosphate pathway (PPP) enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH). Moreover, we show that cisplatin-resistant cells are more sensitive to G6PDH inhibition. Even if the metabolomic fingerprint of ovarian cancer cells remains to be further elucidated, these findings indicate that PPP offers innovative potential targets to overcome cisplatin resistance.

Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation; supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50-1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples, LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic alterations.

The new criteria for diagnosing gestational diabetes identified a group of women previously classifiable as normal according to the 4th International Workshop Conference criteria, but revealing metabolic characteristics and pregnancy outcomes resembling those of women who would have been considered to have gestational diabetes by the previous criteria.