In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.
Pharmacologic inhibition of host Phosphodiesterase-4 improves isoniazid-Mediated clearance of Mycobacterium tuberculosis

Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.99.4 vs 44.415.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. : Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients.
Potential Factors for Prediction of Disease Severity of COVID-19 Patients

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments. Between 2002 and 2003, severe acute respiratory syndrome (SARS) caused by coronavirus (SARS-CoV) affected over 30 countries on five continents. Soon after, HCoV-NL63 was identified in a seven-month-old infant with bronchiolitis and conjunctivitis in 2004 1 , and followed by HCoV-HKU1 in 2005 2 . Later, the Middle East Respiratory Syndrome coronavirus (MERS-CoV) rapidly spread worldwide with fatality rates up to 30% 3 . Several reports have recently demonstrated the existence of a SARS-like coronavirus, which indicates that coronavirus-associated respiratory tract infections continue to have a significant epidemic potential 4-6 . Therefore, there remains an urgent requirement for standardization of treatments in order to develop more effective interventional strategies for coronavirus-associated diseases. Clinical treatments implemented following the sudden outbreak of SARS-CoV included empirical and experimental types, although their effectiveness and side effects remain controversial. Antiviral drugs, including ribavirin, lopinavir, and ritonavir, were prescribed soon after SARS-CoV was identified as the causative agent 7, 8 . Type I interferon was also used owing to its inhibitory effect on SARS-CoV replication 9 . Furthermore, the use of convalescent plasma or immunoglobulin was reported for the treatment of SARS 10 . More frequently, corticosteroids, including methylprednisolone alone or in combination with antiviral drugs, were administered to SARS patients to prevent immunopathological lung damage 11 , although the timing and dosage regimens for steroid administration were controversial 12, 13 . The administration of high-dose pulses of methylprednisolone has been associated with psychic derangements, acute myopathy, and osteonecrosis [14] [15] [16] . Considering the fact that these disorders usually progress to a chronic state, we propose that the SARS survivors may suffer from metabolic disturbances, Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIeNTIfIC REPORTS | 7: 9110 |
Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection OPEN