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2022 ◽  
Vol 9 ◽  
Author(s):  
Ponnusamy Packialakshmi ◽  
Perumal Gobinath ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
Raman Gurusamy ◽  
...  

In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (1H—13C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI50 value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC50 > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an in-silico study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (−5.9 kcal/mol) and a lower binding affinity for Doxorubicin (−5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Shilpa P. Pothapragada ◽  
Praver Gupta ◽  
Soumi Mukherjee ◽  
Tamal Das

AbstractIn epithelia, normal cells recognize and extrude out newly emerged transformed cells by competition. This process is the most fundamental epithelial defence against cancer, whose occasional failure promotes oncogenesis. However, little is known about what factors determine the success or failure of this defence. Here we report that mechanical stiffening of extracellular matrix attenuates the epithelial defence against HRasV12-transformed cells. Using photoconversion labelling, protein tracking, and loss-of-function mutations, we attribute this attenuation to stiffening-induced perinuclear sequestration of a cytoskeletal protein, filamin. On soft matrix mimicking healthy epithelium, filamin exists as a dynamically single population, which moves to the normal cell-transformed cell interface to initiate the extrusion of transformed cells. However, on stiff matrix mimicking fibrotic epithelium, filamin redistributes into two dynamically distinct populations, including a new perinuclear pool that cannot move to the cell-cell interface. A matrix stiffness-dependent differential between filamin-Cdc42 and filamin-perinuclear cytoskeleton interaction controls this distinctive filamin localization and hence, determines the success or failure of epithelial defence on soft versus stiff matrix. Together, our study reveals how pathological matrix stiffening leads to a failed epithelial defence at the initial stage of oncogenesis.


2022 ◽  
Vol 10 (1) ◽  
pp. 95
Author(s):  
Wanli Peng ◽  
Yanqiu Wang ◽  
Yali Fu ◽  
Zixin Deng ◽  
Shuangjun Lin ◽  
...  

Tellurite is highly toxic to bacteria and commonly used in the clinical screening for pathogens; it is speculated that there is a potential relationship between tellurite resistance and bacterial pathogenicity. Until now, the core function genes of tellurite resistance and their characteristics are still obscure. Pseudomonas citronellolis SJTE-3 was found able to resist high concentrations of tellurite (250 μg/mL) and formed vacuole-like tellurium nanostructures. The terZABCDE gene cluster located in the large plasmid pRBL16 endowed strain SJTE-3 with the tellurite resistance of high levels. Although the terC and terD genes were identified as the core function genes for tellurite reduction and resistance, the inhibition of cell growth was observed when they were used solely. Interestingly, co-expression of the terA gene or terZ gene could relieve the burden caused by the expression of the terCD genes and recover normal cell growth. TerC and TerD proteins commonly shared the conserved sequences and are widely distributed in many pathogenic bacteria, highly associated with the pathogenicity factors.


Author(s):  
Shimo Yu ◽  
Shining Wu ◽  
Jing Zhang ◽  
Xinfu Zhao ◽  
Xiaochan Liu ◽  
...  

The interactions between organelles can maintain normal cell activity. Lysosomes, as waste disposal systems of cells, have many important interactions with plasma membrane, especially in the repairing of cracked plasma...


Author(s):  
Malak Abdulrahman Seid Ahmed ◽  
Nazik Omer ◽  
Ahmed M. Suliman ◽  
Mona Ellaithi

Background: Cyclin D1 expression regulates normal cell cycle. Its deregulation or overexpression may cause disruption in the normal cell cycle control and lead to cancer progression. In this study, we aimed to study the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and find its association with the different grades of oral tumors, if any.  Methods: This cross-sectional study included 40 formalin-fixed paraffin-embedded tissue blocks specimens of OSCC with variable grades. The expression of cyclin D1 was evaluated through immunohistochemical (IHC) staining. Results: There were 9 female and 31 male samples, with a male-to-female ratio of 3.4:1. The age ranged between 25 and 90 years with an average age of 65.5 years. Twenty-five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (WDSCC) and fifteen (37.5%) as poorly differentiated squamous cell carcinoma (PDSCC). No cases of moderately differentiated squamous carcinoma were included in the study. The expression of cyclin D1 was detected in the cases of WDSCC and a lesser expression was seen in the PDSCC with a P-value of 0.0003, OR 1581 and 95% CI (29.8239 to 83810.7113). Conclusion: Cyclin D1 is expressed in  OSCC and stronger expression was detected in WDSCC.


2021 ◽  
Vol 22 (24) ◽  
pp. 13669
Author(s):  
Kinga Paruch ◽  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Hordyjewska ◽  
Łukasz Popiołek

Antibiotic resistance is now a global problem, and the lack of effective antimicrobial agents for the treatment of diseases caused by resistant microbes is increasing. The 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines presented in this article may provide a good starting point for the development of potential new effective antimicrobial agents useful in the treatment of bacterial and fungal infections. Particular attention is drawn to the 1,3,4-oxadiazole derivative marked with the number 29 with 5-nitrofuran-2-yl substituent in its chemical structure. This substance showed a strong bactericidal effect, especially against Staphylococcus spp., and no cytotoxicity to the L929 normal cell line.


2021 ◽  
Vol 15 (12) ◽  
pp. 3325-3327
Author(s):  
Nasreen Ali ◽  
Hina Hussain

Aim: To study the electroencephalogram changes in children with acute encephalitis. Study design: Cross-sectional study. Place and duration of study: The cases were admitted from OPD and emergency over duration of 10 months from May2009 to March 2010 in Children Hospital PIMS, Islamabad. Method: Patients with Cerebral Palsy, Degenerative Brain disease, Cerebral Malaria and Meningitis were excluded. Written informed consent was taken from parents /guardians. All patients, from both genders, age varying from 4 months to 12 years, fitting the criteria of Acute Encephalitis according to ICD 9 & 10 were included in the study, which were 56 in total. All cases had Lumbar puncture and Cerebro Spinal Fluid examination. The findings of pleocytosis (WBC count more than5 u/l), protein and sugar were recorded. EEG (Electroencecephlogram) was done in 52 patients, frequencies and percentages were calculated of the findings. Results: The mean age was 4. 6 years, (varying from 4 months to 12 years) with a standard deviation of 3. 2. From a total of fifty six patients, 38(68%) were males and 18(32%) females. All cases presented with fever (100%). Cerebro Spinal Fluid examination, showed Pleocytosis in 30(54%) while 46(46%) had normal cell count. Cerebro Spinal Fluid protein content was normal in 45(80%) and increased in 11(20%). Cerebro Spinal Fluid sugar was normal in 50(89%) and 6(11%) had low. Electroencephalogram was done in fifty-two patients out of which 30(58%) were normal, 22(42%) were abnormal. Intermittent slowing was found in 17(77%) and 5(23%) cases had focal discharges along with intermittent slowing, out of which three were unilateral temporo-frontal discharges, two cases had other focal discharges on EEG. Conclusion: In patients with Acute Encephalitis, slowing of the rhythm was the most frequent abnormal Electroencephalogram finding, followed by focal discharges in children admitted in Children’s Hospital PIMS, Islamabad. Keywords: Acute Encephalitis, Electroencephalogram (electro encephalogram), Cerebro Spinal Fluid Pleocytosis, Fever


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7228
Author(s):  
Jingjing Li ◽  
Yan Lin ◽  
Lei He ◽  
Rongxiu Ou ◽  
Tao Chen ◽  
...  

Sophora flavescens is a regularly used traditional Chinese medicine. In an attempt to discover adequate active agents, the isoprenoid flavonoids from S. flavescens were further investigated. In this work, two new compounds (1–2, kurarinol A-B) together with 26 known ones (3–28) were isolated and elucidated on the basis of extensive NMR, UV and MS analyses. Furthermore, the antioxidant activity of all constituents was assessed through ABTS, PTIO and DPPH methodologies and also were evaluated for cytotoxic activity by three tumor cell lines (HepG2, A549 and MCF7) and one human normal cell line (LO2 cells). As a result, a multitude of components revealed significant inhibitory activity. In particular, compound 1–2 (kurarinol A-B), two new flavanonols derivatives, exhibited the most potent ABTS inhibitory activity with IC50 of 1.21 µg/mL and 1.81 µg/mL, respectively. Meanwhile, the new compound 1 demonstrated remarkable cytotoxicity against three cancer cells lines with IC50 values ranging from 7.50–10.55 μM but showed little effect on the normal cell. The two new isoprenoid flavonoids could be promising antioxidant and anti-tumor nature agents.


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