Pengaruh Iradiasi Gamma Pada Aktivitas Sitotoksik Daging Buah Mahkota Dewa (Phaleria Macrocarpa (Scheff) Boerl.)

Iradiasi gamma telah digunakanoleh industri obat herbal untuk pengawetan simplisia tanaman obat, tetapi pengaruh iradiasiterhadap khasiatnya belum diteliti. Tujuan penelitian adalah memperoleh dosis iradiasi optimaluntuk pengawetan simplisia daging buah mahkota dewa tanpa merusak khasiatnya. Telahdilakukan iradiasi gamma terhadap simplisia daging buah kering mahkota dewa pada variasidosis 0; 5; 7,5 ; 10; 15; 20 kGy. Cemaran mikroba diuji dengan metode yang mengacu padaSNI, yang menunjukkan bahwa dosis 5 kGy telah dapat membunuh seluruh mikroba. Masingmasingsampel dimaserasi dengan etanol, lalu ekstrak yang diperoleh difraksinasi dengankromatografi kolom, diperoleh 8 fraksi. Uji sitotoksisitas fraksi-fraksi terhadap sel leukemiaL1210 menunjukkan bahwa Fr.3 merupakan fraksi paling sitotoksik. Untuk menentukan dosisiradiasi optimal dalam menghambat pertumbuhan serta membunuh semua bakteri dankapang/khamir pada simplisia daging buah mahkota dewa tanpa menurunkan aktivitassitotoksik, dilakukan analisis kromatografi lapis tipis (KLT) dan kromatografi cair kinerja tinggi(KCKT) terhadap Fr.3. Hasil penelitian menunjukkan bahwa iradiasi dengan dosis > 5 kGy padasimplisia daging buah mahkota dewa dapat menghambat pertumbuhan dan membunuh semuabakteri serta kapang khamir yang ada tanpa menurunkan aktivitas sitotoksik ekstrak etanolsecara nyata terhadap sel leukemia L1210. Penurunan aktivitas sitotoksik ekstrak etanolterhadap sel leukemia L1210 secara nyata terjadi setelah iradiasi pada dosis > 10 kGy. Padadosis 10 kGy, aktivitas sitotoksik sudah terlihat menurun meskipun belum melampaui batassuatu fraksi dinyatakan tidak aktif dan hasil analisis profil kromatogram KLT menunjukkanbahwa Fr. 3 sedikitnya mengandung 10 komponen. Iradiasi sampai dengan dosis 20 kGymengakibatkan intensitas salah satu puncak mayor menurun, dan penurunannya sebandingdengan besarnya dosis. Dosis 5 sampai 10 kGy merupakan dosis optimum untuk tujuanpengawetan tanpa merusak aktivitas sitotoksiknya

Modes of Overinitiation, dnaA Gene Expression, and Inhibition of Cell Division in a Novel Cold-Sensitive hda Mutant of Escherichia coli

The chromosomal replication cycle is strictly coordinated with cell cycle progression in Escherichia coli. ATP-DnaA initiates replication, leading to loading of the DNA polymerase III holoenzyme. The DNA-loaded form of the {beta} clamp subunit of the polymerase binds the Hda protein, which promotes ATP-DnaA hydrolysis, yielding inactive ADP-DnaA. This regulation is required to repress overinitiation. In this study, we have isolated a novel cold-sensitive hda mutant, the hda-185 mutant. The hda-185 mutant caused overinitiation of chromosomal replication at 25{degrees}C, which most likely led to blockage of replication fork progress. Consistently, the inhibition of colony formation at 25{degrees}C was suppressed by disruption of the diaA gene, an initiation stimulator. Disruption of the seqA gene, an initiation inhibitor, showed synthetic lethality with hda-185 even at 42{degrees}C. The cellular ATP-DnaA level was increased in an hda-185-dependent manner. The cellular concentrations of DnaA protein and dnaA mRNA were comparable at 25{degrees}C to those in a wild-type hda strain. We also found that multiple copies of the ribonucleotide reductase genes (nrdAB or nrdEF) or dnaB gene repressed overinitiation. The cellular levels of dATP and dCTP were elevated in cells bearing multiple copies of nrdAB. The catalytic site within NrdA was required for multicopy suppression, suggesting the importance of an active form of NrdA or elevated levels of deoxyribonucleotides in inhibition of overinitiation in the hda-185 cells. Cell division in the hda-185 mutant was inhibited at 25{degrees}C in a LexA regulon-independent manner, suggesting that overinitiation in the hda-185 mutant induced a unique division inhibition pathway

PENGARUH IRADIASI GAMMA PADA AKTIVITAS SITOTOKSIK DAGING BUAH MAHKOTA DEWA (Phaleria macrocarpa (Scheff) Boerl.)

Iradiasi gamma telah digunakanoleh industri obat herbal untuk pengawetan simplisia tanaman obat, tetapi pengaruh iradiasiterhadap khasiatnya belum diteliti. Tujuan penelitian adalah memperoleh dosis iradiasi optimaluntuk pengawetan simplisia daging buah mahkota dewa tanpa merusak khasiatnya. Telahdilakukan iradiasi gamma terhadap simplisia daging buah kering mahkota dewa pada variasidosis 0; 5; 7,5 ; 10; 15; 20 kGy. Cemaran mikroba diuji dengan metode yang mengacu padaSNI, yang menunjukkan bahwa dosis 5 kGy telah dapat membunuh seluruh mikroba. Masingmasingsampel dimaserasi dengan etanol, lalu ekstrak yang diperoleh difraksinasi dengankromatografi kolom, diperoleh 8 fraksi. Uji sitotoksisitas fraksi-fraksi terhadap sel leukemiaL1210 menunjukkan bahwa Fr.3 merupakan fraksi paling sitotoksik. Untuk menentukan dosisiradiasi optimal dalam menghambat pertumbuhan serta membunuh semua bakteri dankapang/khamir pada simplisia daging buah mahkota dewa tanpa menurunkan aktivitassitotoksik, dilakukan analisis kromatografi lapis tipis (KLT) dan kromatografi cair kinerja tinggi(KCKT) terhadap Fr.3. Hasil penelitian menunjukkan bahwa iradiasi dengan dosis > 5 kGy padasimplisia daging buah mahkota dewa dapat menghambat pertumbuhan dan membunuh semuabakteri serta kapang khamir yang ada tanpa menurunkan aktivitas sitotoksik ekstrak etanolsecara nyata terhadap sel leukemia L1210. Penurunan aktivitas sitotoksik ekstrak etanolterhadap sel leukemia L1210 secara nyata terjadi setelah iradiasi pada dosis > 10 kGy. Padadosis 10 kGy, aktivitas sitotoksik sudah terlihat menurun meskipun belum melampaui batassuatu fraksi dinyatakan tidak aktif dan hasil analisis profil kromatogram KLT menunjukkanbahwa Fr. 3 sedikitnya mengandung 10 komponen. Iradiasi sampai dengan dosis 20 kGymengakibatkan intensitas salah satu puncak mayor menurun, dan penurunannya sebandingdengan besarnya dosis. Dosis 5 sampai 10 kGy merupakan dosis optimum untuk tujuanpengawetan tanpa merusak aktivitas sitotoksiknya

Compensatory mechanisms in adult degenerative thoracolumbar spinal deformity – Radiographic patterns, their reversibility after corrective surgery, and the influence of pelvic morphology

Objective: Loss of lumbar lordosis (LL) in degenerative deformity activates spinal compensatory mechanisms to maintain neutral C7 sagittal vertical axis (C7SVA), such as an increase in pelvic tilt (PT) and decreased thoracic kyphosis (TK). We study the extent to which PT increase and TK reduction contribute to the compensation of pelvic incidence (PI)-LL mismatch. Methods: A cohort of 43 adult patients with adult degenerative thoracolumbar deformity were included in this retrospective study. Radiographic spinopelvic measurements were obtained before and after corrective surgery. Pearson correlations were calculated. Results: Preoperative PI-LL mismatch significantly correlated with an increase in PT and a decrease in TK in the whole cohort r = +0.66 (95% confidence interval [CI] 0.44–0.8) and r = −0.67 (95% CI − 0.81–−0.47), respectively, at a relative rate of 0.37 (standard deviation [SD]: 0.07) and − 0.57 (SD: 0.09), respectively. In patients with low PI, only TK showed a significant correlation with PI-LL mismatch, r = −0.56 (95% CI − 0.8 to − 0.16), at a rate of − 0.57 (SD: 0.19). The high PI subgroup showed a significant correlation with PT, TK, and C7SVA, r = 0.62 (95% CI 0.26–0.82), r = −0.8 (95% CI − 0.9–−0.58), and r = 0.71 (95% CI 0.41–0.87) at rates of 0.48 (SD: 0.11), −0.72 (SD: 0.12), and 0.62 (SD: 1.27). Conclusions: Decreased TK represented a more consistent compensatory mechanism in patients with high and low PI when compared to an increase in PT. PI-LL mismatch induced more pronounced changes in TK than did PT in both subgroups. Patients with high PI relied more on increases in PT and a relative decrease in TK to compensate for PI-LL mismatch than patients with low PI. Keywords: Adult spinal deformity, pelvic incidence, pelvic tilt, sagittal balance, thoracolumbar deformit

The Extended Lateral Supraorbital Approach and Extradural Anterior Clinoidectomy Through a Frontopterio-Orbital Window : Technical Note and Pilot Surgical Series

BACKGROUND: Lateral approaches to treat anterior cranial fossa lesions have evolved since the first frontotemporal approach described by Dandy in 1918. We describe a less invasive approach to perform extradural anterior clinoidectomy through a lateral supraorbital (LSO) approach for anterior circulation aneurysms and anterolateral skull base lesions. METHODS: The extended LSO approach involves performing a standard lateral supraorbital craniotomy followed by drilling of the sphenoid wing and lateral wall of the orbit through the frontal bony opening of the LSO approach, without any temporal extension of the craniotomy. This creates a frontopterio-orbital window exposing the periorbita; superior, medial, and anterior aspect of the temporal dura mater; and superior orbital fissure. After unroofing the superior orbital fissure, the meningo- orbital fold is cut, and the temporal dura mater is peeled from the lateral wall of the cavernous sinus to expose the anterior clinoid process allowing a standard opening of the optic canal and anterior clinoidectomy. RESULTS: The extended LSO approach and extradural anterior clinoidectomy allowed access to 4 sphenoid wing/anterior clinoidal meningiomas, 5 anterior circulation aneurysms, 2 temporomesial lesions, and 1 orbital/cavernous sinus abscess. Postoperatively, 2 patients had transient hemiparesis, 2 patients had transient third nerve palsy, and 1 patient had minimal visual field deterioration. All patients had a modified Rankin Scale score CONCLUSION: The extended LSO approach opens a new route (frontopterio-orbital window) to perform extradural anterior clinoidectomy safely and increases surgical exposure, angles, and operability of a less invasive keyhole craniotomy (LSO approach) to treat anterior cranial fossa lesions.Peer reviewe

FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients

Extensive extracellular matrix production and increased cell-matrix adhesion by bone marrow stromal cells (BMSCs) are hallmarks of fibrotic alterations in the vertebral bone marrow known as Modic type 1 changes (MC1). MC1 are associated with non-specific chronic low-back pain. To identify treatment targets for MC1, in vitro studies using patient BMSCs are important to reveal pathological mechanisms. For the culture of BMSCs, fibroblast growth factor 2 (FGF2) is widely used. However, FGF2 has been shown to suppress matrix synthesis in various stromal cell populations. The aim of the present study was to investigate whether FGF2 affected the in vitro study of the fibrotic pathomechanisms of MC1-derived BMSCs. Transcriptomic changes and changes in cell-matrix adhesion of MC1-derived BMSCs were compared to intra-patient control BMSCs in response to FGF2. RNA sequencing and quantitative real-time polymerase chain reaction revealed that pro-fibrotic genes and pathways were not detectable in MC1-derived BMSCs when cultured in the presence of FGF2. In addition, significantly increased cell-matrix adhesion of MC1-derived BMSCs was abolished in the presence of FGF2. In conclusion, the data demonstrated that FGF2 overrides key pro-fibrotic features of MC1 BMSCs in vitro. Usage of FGF2-supplemented media in studies of fibrotic mechanisms should be critically evaluated as it could override normally dominant biological and biophysical cues

Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Background: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to- hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. Methods: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. Results: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02–1.21) for BMI, 1.13 (95% CI 1.04–1.23) for WC, 1.09 (95% CI 0.98–1.21) for HC, and 1.15 (95% CI 1.00–1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer ( P interaction o 0.001), where never HT users showed an B 20% increased risk per s.d. of BMI, WC, and HC compared to ever users. Conclusions: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use