Pulmonary fibrosis is an important health problem; one of the drugs used in its treatment is pirfenidone (PFD). Fisetin (FST) is a flavonoid with antioxidative, anti-inflammatory, and antifibrotic effects. The aim of this study was to induce PF in rats with bleomycin (BLM) and to investigate the combined effect of PFD and FST in the treatment of fibrosis. In the study, 40 male Wistar rats were divided into five groups (n = 8). Sham group was administered saline on day 0 and BLM (5 mg/kg, i.t.) was administered to the other groups; BLM + PFD group: PFD (50 mg/kg) was administered every day between the first and 15th days; BLM + FST group: FST (25 mg/kg) was administered between the first and 15th days; BLM + PFD + FST group: PFD (50 mg/kg) and FST (25 mg/kg) were administered by gavage every day between the first and 15th days. At the end of the 15th day, BAL was performed under anaesthesia and lung tissues were removed. Histopathological, biochemical, and RT-PCR analyses were performed in the lung tissue. In our study, the concomitant use of FST and PFD caused downregulation of NF-κB p65, TGF-β1, and α-SMA expressions; downregulation of TIMP-1, MMP-2, and MMP-9 genes; downregulation of HYP, MPO, and MDA activity; decrease in the number of differential cells in BAL; and upregulation of GSH. This shows that FST and PFD have antifibrotic, antioxidative, and anti-inflammatory effects. Our results show that the combined use of PFD and FST in BLM-induced pulmonary fibrosis reduces extracellular matrix accumulation, downregulates the level of gelatinases and their inhibitors, and provides significant improvements in antioxidative defence parameters.

Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. Treatments are extremely scarce; therapeutic drugs and transplantation therapies are not widely available due to cost and a lack of donors, respectively. Recently, there has been a high interest in regenerative medicine and exponential advancements in stem cell-based therapies have occurred. However, a sensitive imaging technique for investigating the in vivo dynamics of transplanted stem cells has not yet been established and the mechanisms of stem cell-based therapy remain largely unexplored. In this study, we administered mouse adipose tissue-derived mesenchymal stem cells (mASCs) labeled with quantum dots (QDs; 8.0 nM) to a mouse model of bleomycin-induced pulmonary fibrosis in an effort to clarify the relationship between in vivo dynamics and therapeutic efficacy. These QD-labeled mASCs were injected into the trachea of C57BL/6 mice seven days after bleomycin administration to induce fibrosis in the lungs. The therapeutic effects and efficacy were evaluated via in vivo/ex vivo imaging, CT imaging, and H&E staining of lung sections. The QD-labeled mASCs remained in the lungs longer and suppressed fibrosis. The 3D imaging results showed that the transplanted cells accumulated in the peripheral and fibrotic regions of the lungs. These results indicate that mASCs may prevent fibrosis. Thus, QD labeling could be a suitable and sensitive imaging technique for evaluating in vivo kinetics in correlation with the efficacy of cell therapy.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin\'s lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.

OBJECTIVE: Tuberostemonine has several biological activity, the aim of study examined the impact of tuberostemonine on the proliferation of TGF-β1 induced cell model, and its ability to alleviate pulmonary fibrosis stimulated by bleomycin in mice.
METHODS: In vitro, we assessed the effect of tuberostemonine (350, 550 and 750 µM) on the proliferation of cells stimulated by TGF-β1 (10 μg/L), as well as on parameters such as α-SMA vitality, human fibronectin, collagen, and hydroxyproline levels in cells. In vivo, we analyzed inflammation, hydroxyproline, collagen activity and metabolomics in the lungs of mice. Additionally, a comprehensive investigation into the TGF-β/smad signaling pathway was undertaken, targeting lung tissue as well as HFL cells.
RESULTS: Within the confines of an in vitro setup, the tuberostemonine manifested a discerned IC50 of 1.9 mM. Furthermore, a significant reduction of over fifty percent was ascertained in the secretion levels of hydroxyproline, fibronectin, collagen type I, collagen type III and α-SMA. In vivo, tuberostemonine obviously improved the respiratory function percentage over 50% of animal model and decreased the hydroxyproline, lung inflammation and collagen deposition. A prominent decline in TGF-β/smad pathway functioning was identified within both the internal and external cellular contexts.
CONCLUSIONS: Tuberostemonine is considered as a modulator to alleviate fibrosis and may become a new renovation for pulmonary fibrosis.

UNASSIGNED: The impaired proliferative capacity of alveolar epithelial cells after injury is an important factor causing epithelial repair dysfunction, leading to the occurrence of idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells as the stem cells of alveolar epithelium participate in the repair process after alveolar injury. Lipocalin-2 (LCN2) participates in multiple processes regulating the pathological process of alveolar epithelial cells, but the mechanisms involved are still unclear.
UNASSIGNED: We used a BLM-treated mouse model to characterize the expression of LCN2 in lung fibrosis regions and analyzed the location of LCN2 in alveolar epithelial cells. Moreover, human pulmonary alveolar epithelial cells (HPAEpiCs) were transfected with the LCN2 overexpression plasmid vector in vitro. Recombinant human interleukin-17 (IL-17) protein (rhIL-17) at different concentrations was administered to intervene in HPAEpiCs, observing cell viability and analyzing the concentration-dependent effect of IL-17.
UNASSIGNED: LCN2 was increased in the alveolar epithelium post-BLM injury, and highly expressed LCN2 was mainly concentrated on AT2 cells in BLM-injured lungs. Meanwhile, LCN2-overexpressing HPAEpiCs showed impaired cell viability and cell growth. HPAEpiC intervention with rhIL-17 mildly rescued the impaired cell proliferation induced by LCN2 overexpression, and the effect of IL-17 intervention was partially concentration-dependent.
UNASSIGNED: The results revealed the reversed effect of IL-17 on the impaired proliferative capacity of the alveolar epithelium induced by LCN2 overexpression. The target alveolar epithelial cells regulated by this process were AT2 cells, providing new clues for alveolar epithelium repair after injury and the treatment of lung injury diseases.

Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.

Cancer remains one of the leading causes for death worldwide. Palliative chemotherapy is vital for certain cancer patients, highlighting the critical need for treatment monitoring tools to prevent drug accumulation and mitigate the risk of high toxicity. Therefore, our aim was to evaluate the potential of screen-printed electrodes for the development of sensitive and accurate biosensors for the detection/quantification of antineoplastic drugs. To this purpose, we developed a cisplatin sensor. By functionalizing the gold electrode with human serum albumin and by collecting the electrochemical signal obtained in a H2O2 solution, through voltammetry measurements, we were able to correlate the current measured at 430 mV with the concentration of cisplatin present in human serum samples, with a correlation coefficient of R2 = 0.99. Also, a bleomycin biosensor was developed and proven functional, but further optimization steps were employed in order to improve the accuracy. The developed biosensors have a detection range of 0.0006-43.2 mg/mL for cisplatin and 0.23-7.56 μg/mL for bleomycin in the serum samples. Our preliminary results show that these biosensors can facilitate the real-time monitoring of cisplatin and bleomycin serum levels, allowing healthcare professionals to tailor treatment strategies based on individual patient responses.

Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-β1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-β1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.

The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-β-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.